The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome, because the tear film represents the interface between the eye and the environment. Despite having a multifactorial origin, the main risk factors for the emergence of the ocular disease are female gender and advanced age. Likewise, morphological changes in several glands and in chemical composition of their secretions such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors to maintain a condition of good health of the ocular anterior segment. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic infiammation that reflex on the ocular surface. However, it is one of the most commonly encountered disease in clinical practice and many other causes related to daily life and to lengthen the average life will contribute to the beginning. This review will consider how and what disorders of the ocular surface are responsible for a widespread pathology so. In the end, the most appropriate and new therapies will be briefly exposed according to the specific pathology.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

Purpose. Moraxella is an ocular bacterial pathogen isolated in cases of keratitis, conjunctivitis, and endophthalmitis. Gram-negative brick-shaped diplobacilli from ocular specimens, and slow growth in culture, are early indications of Moraxella ocular infection; however, identifying Moraxella to species can be complex and inconsistent. Methods. In this study, bacteria consistent with Moraxella were identified to species using: 1) DNA sequencing coupled with vancomycin susceptibility, 2) MALDI-TOF Mass Spectrometry, and 3) Biolog ID System. Study samples consisted of 9 ATCC Moraxella controls, 82 isolates from keratitis, 21 isolates from conjunctivitis, and 4 isolates from endophthalmitis. Results. The ATCC controls were correctly identified. For keratitis, 66 (80.5%) were identified as M. nonliquefaciens, 7 (9.0%) as M. lacunata, 5 (6%) as M. osloensis, 2 (2.5%) as Acinetobacter lwoffi, 1 (1.0%) as M. bovis/nonliquefaciens, and 1 (1.0%) as M. osloensis/nonliquefaciens. For conjunctivitis, 9 (43.0%) were identified as M. osloensis, 6 (29.0%) as M. nonliquefaciens, 3 (14.3%) as Roseomonas, 2 (9.5%) as Acinetobacter (parvus, junii), and 1 (4.5%) as M. catarrhalis/M. nonliquefaciens. From endophthalmitis, 3 of 4 of the isolates were M. nonliquefaciens. Overall, M. nonliquefaciens and M. osloensis were identified in 70% (75 of 107) and 13% (14 of 107) of cases, respectively, totaling 83% (89 of 107). Conclusions. M. nonliquefaciens and M. osloensis are important bacterial pathogens of the eye as determined by DNA sequencing, MALDI-TOF MS, and Biolog. Although Moraxella catarrhalis is a clinical pathogen, other species of Moraxella appear to have a prominent role in eye infections.

Background: To assess the incidence and characteristic of cataract surgery in Poland from 2010 to 2015 and to interpret these findings. Patients and methods: Data from all patients who underwent cataract surgery alone or in combined procedures in Poland between January 2010 and December 2015 were evaluated. Patient data were from the national database of hospitalizations maintained by National Health Fund, data on the population of Poland were obtained from Central Statistical Office of Poland. Results: In total 1,218,777 cataract extractions (alone or combined with other procedures) were performed in 1,081,345 patients during 2010 -2015. Overall, the incidence of cataract surgery increased from 5.22/1000 person-years in year 2010 to 6.17/1000 person-years in year 2015. Phacoemulsification was performed in 97.46% of cataract extractions, and 3.02% of cataract extractions were combined procedures. The rate of one-day procedures increased from 28.3% in year 2010 to 43.1% in year 2015. The probability of second-eye surgery 12 months after the first-eye surgery increased from 44% in 2010 to 73% in 2015 (log-rank test p<0.0001). Conclusion: In Poland, from 2010 to 2015 the total incidence of cataract surgery, the number of people who underwent surgery, and the numbers of one-day and combined cataract surgeries, increased significantly.

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

HLA class I alleles constitute established risk factors for non-infectious uveitis and preemptive genotyping of HLA class I alleles is standard practice in the diagnostic work-up. The HLA-A29 serotype is indispensable to Birdshot Uveitis (BU) and renders this enigmatic eye condition a unique model to better understand how the antigen processing and presentation machinery contributes to non-infectious uveitis or chronic inflammatory conditions in general. This review will discuss salient points regarding the protein structure of HLA-A29 using and how key amino acid positions impact the peptide binding preference and interaction with T cells. We discuss to what extent the risk genes ERAP1 and ERAP2 uniquely affect HLA-A29 and how the discovery of a HLA-A29-specific submotif may impact autoantigen discovery. We further provide a compelling argument to solve the long-standing question why BU only affects HLA-A29-positive individuals from Western-European ancestry by exploiting data from the 1000 Genomes Project. We combine novel insights from structural and immunopeptidomic studies and discuss the functional implications of genetic associations across the HLA class I antigen presentation pathway to refine the etiological basis of Birdshot Uveitis.

Objective: The Rho GTPase/Rho kinase pathway is an important target in glaucoma treatment. This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor developed for cancer treatment, in a porcine ex vivo pigmentary glaucoma model. Materials and Methods: Twenty-eight fresh porcine anterior chambers were perfused with pigment medium (1.67 × 10⁷ pigment particles/mL) for 48 hours before being subjected to the RKI-1447 (n = 16) or the vehicle control (n = 12). Another twelve eyes with normal medium perfusion served as the control. The intraocular pressure (IOP) was recorded at two-minute intervals and the outflow facility was calculated. To investigate the intracellular mechanism of the IOP reduction, primary trabecular meshwork cells were exposed to RKI-1447 or the vehicle control and then analyzed for changes in cytoskeleton, motility, and phagocytosis. Results: Compared to the baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 exhibited no apparent changes in the micro- or macroscopic appearance, including histology. Primary TM cells exposed to RKI-1447 showed a significant disruption of the actin cytoskeleton both in the presence and absence of pigment exposure (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI reversed. Conclusions: RKI-1447 is a novel ROCK inhibitor that significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it especially useful for the treatment of secondary glaucomas with an increased phagocytosis load but also for other open angle glaucomas.

Purpose: To compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination in newly diagnosed primary open angle glaucoma patients. Methods: In this prospective, interventional case series, newly diagnosed primary open angle glaucoma (POAG) patients that had not been treated for glaucoma were included. Patients were started on Cosopt twice a day (BID) for 1 month and then switched to three times a day (TDS) for additional 1 month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP) and 24-hours heart rate (HR) measurements at baseline, month 1( BID), and month 2( TDS). IOP, systolic and diastolic pressures were measured at 8:00 AM,12:00 AM, 4:00 PM, 8:00 PM and 12:00 PM. Throughout the study, all adverse events were recorded and monitored by the investigators. Results: In 31 POAG patients that completed the study ,mean baseline IOP was 23.1±3.15 mmHg . IOP was decreased significantly 16.5 ± 2.21 at 1 month (P < 0.0001) and 13.9 ± 2.23 mmHg at 1 and 2 month follow up. (P < 0.0001) IOP was significantly lower in month 2 compared to month 1 (P = 0.0004). While Cosopt BID significantly reduced the mean 24-hour systolic BP and mean 24-hour HR from baseline (P < 0.0001), the mean 24-hour systolic BP and HR remained unchanged 2ith Cosopt TDS compared to BID (P = 0.62). Conclusions: Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profile.

To evaluate the 2-year efficacy and safety of ab interno trabeculectomy with the Trabectome in Chinese primary open-angle glaucoma (POAG) patients. This was a multicenter, retrospective study and included POAG patients with or without visually-significant cataracts. The primary outcome was intraocular pressure (IOP) reduction. Secondary outcomes included reduction of glaucoma medications, surgical complications, and success at 2-years. Success was defined as: 1) IOP < 21 mmHg and at least 20% IOP reduction from baseline after 3 months at any two consecutive visits, and 2) no additional glaucoma surgery required. A total of 42 patients were enrolled; thirteen had a history of failed glaucoma surgery. Twelve patients underwent Trabectome surgery combined with phacoemulsification while the remainder underwent Trabectome surgery alone. Overall, the mean preoperative IOP was 21.4±1.23 mmHg. The Trabectome lowered IOP to 18.5± 0.94 mmHg at 2 years (P<0.05). The number of glaucoma medications also decreased from a baseline of 2.0±0.9 to 1.2± 0.21 at 2 years (P=0.04). The overall success was 78%, with patients undergoing combined surgery having a higher success than those with Trabectome surgery alone (100% vs. 76%). No major complications were seen. The Trabectome appears to be an efficient and safe procedure in Chinese POAG patients in the long-term.

Purpose: To analyze the five-year results of Trabectome ab interno trabeculectomy of a single glaucoma center. Method: In this retrospective interventional single-center case series, data of 93 patients undergoing ab interno trabeculotomy between September 2010, and December 2012 were included. Kaplan-Meier analysis was performed using success criteria defined as postoperative intraocular pressure (IOP) ≤21 mm Hg, or >20% reduction from preoperative IOP, and no need for further glaucoma surgery. Risk factors for failure were identified using Cox proportional hazards ratio (HR). Results: The retention rate for five years follow-up was 66%. The cumulative probability of success at 1, 2, 3, 4 and 5 years was 82.6%, 76.7%, 73.9%, 72.3%, and 67.5%. Risk factors for failure were lower baseline IOP (HR=0.27, P=0.001), younger age (HR=0.25, P=0.02), and higher central corneal thickness (HR=0.18, P= 0.01). Pseudoexfoliation was associated with a higher success rate (HR= 0.39, P=0.02). IOP was decreased significantly from 20.0±5.6 mmHg at baseline to 15.6±4.6 mmHg at 5-year follow-up (P=0.001). The baseline number of glaucoma medications was 1.8±1.2, which decreased to 1.0±1.2 medications at 5 years. Conclusion: Trabectome surgery was associated with a good long-term efficacy and safety profile in this single-center case series with a high retention rate. A higher baseline IOP, older age, thinner cornea, and pseudoexfoliation glaucoma were associated with a higher success rate.

Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways leads to the accumulation of lipofuscin and N-retinylidene-N-retinylethanolamine aggregates and chemically-modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as Age-related Macular Degeneration, Stargardt disease and Choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, a-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.

Purpose: To evaluate the efficacy and survival rates of same session ab interno trabeculectomy with the trabectome and Ahmed glaucoma valve implant (AT) in comparison to the Ahmed glaucoma valve alone (A). Method: A total of 107 eyes undergoing primary glaucoma surgery were enrolled in this retrospective comparative case series, including 48 eyes which underwent AT and 59 eyes which received A alone. Participants were identified using the procedural terminology codes, and their medical records were reviewed. The primary outcome measure was surgical success, defined as intraocular pressure (IOP) > 5 mmHg, ≤ 21 mmHg, and IOP reduction ≥ 20% from baseline at two consecutive visits after three months, no reoperation for glaucoma. Secondary outcome measures were IOP, the number of glaucoma medications, incidence of a hypertensive phase, and best corrected visual acuity (BCVA). Results: The cumulative probability of success at one year was 70% in AT, and 65% in A (p=0.85). IOP decreased significantly from 26.6 ± 10.1 mmHg at baseline to 14.7 ± 3.3 mmHg at the final follow-up in AT (p= 0.001). The corresponding numbers for A were 28.8 ± 10.2 and 16.7 ± 4.9, respectively (p= 0.001). The final IOP was significantly lower in AT (p= 0.022). The number of medications at baseline was comparable in both groups (2.6 ± 1.2 in AT and 2.5 ± 1.3 in A, p=0.851). Corresponding number at 1 year visit was 1.2±2 in AT and 2.8±1.8 in A (p=0.001). The incidence of a hypertensive phase was 18.7% in AT and 35.5% in A (p=0.05). HP resolved in only 30% of eyes. The criteria for HP resolution were fulfilled in 9 eyes (30%). There was no difference in the rate of resolution of the hypertensive phase between AT and A (33.3% and 28.5%, respectively, p=0.67). Conclusion: Ahmed glaucoma valve implant with same session trabectome surgery significantly decreased the rate of the hypertensive phase and postoperative IOP as well as the number of glaucoma medications.

Background: To investigate the distribution of refractive errors and their characteristics in older adults. Methods: The study design was cross-sectional study. A total of 1107 men and women were interviewed and underwent detailed ophthalmic examinations, 998 subjects underwent refraction. Myopia was defined as spherical equivalent (SER) refraction ≤ −0.5 dioptres (D) and hyperopia was defined as SER ≥ +0.5 dioptres (D). Results: Among those who were refracted the distribution of myopia and hyperopia was 24.1% (95% CI 21.4–26.7) and 37.5% (95% CI 34.5–40.5), respectively. Myopia decreased from 28.7% in subjects aged 35-59 years to 19.3% in those aged 60 years or older and hyperopia increased from 21.8% at 35–59 years of age to 53.3% in subjects aged ≥60 years. Multiple regression analysis showed decreasing age (OR 0.98, 95% CI 0.96–1.00), female gender (OR 1.87, 95% CI 1.18–2.95) and presence of cataract (OR 2.40 , 95% CI 1.24–4.63) were independent risk factors associated with myopia. Conclusions: The distribution of refractive errors found in our study is similar to those reported in other Caucasian populations and differs from Asian populations. Myopia was positively associated with younger age, female gender and presence of cataract.

To evaluate whether autologous mesenchymal cells, adipose derived stem cells and platelet-rich plasma, grafted into the supracoroideal space by surgical treatment according to Limoli retinal restoration technique (LRRT), can produce growth factors in order to exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and divided based on retinal foveal thickness ≤ 190 or >190 µm into group A and group B, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed an improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of RP, it can be confirmed that further research is needed on tapeto-retinal degenerations both from a clinical and molecular point of view to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation times, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering.

An outbreak of occupational methanol poisoning occurred in small-scale 3rd tier factories of large-scale smartphone manufacturer, in the Republic of Korea, in 2016. To investigate the working environment and the health effect of the methanol exposure among co-workers of the methanol poisoning cases, we performed a cross sectional study on 155 workers at the five aluminum CNC cutting factories. Air and urinary methanol concentration were measured by gas chromatography, and health examination included symptoms, ophthalmological examinations and neurobehavioral tests. Multiple logistic regression analyses controlled for age and sex were conducted for revealing association of employment duration with symptoms. Air concentrations of methanol in factory A and E were ranged from 228.5 to 2220.0 ppm. Mean urinary methanol concentrations of the workers in each factory were from 3.5 mg/L up to 91.2 mg/L. The odds ratios for symptom of deteriorating vision and CNS increased, according to the employment duration, after adjusting for age and sex. Four cases with injured optic nerve and two cases with decreased neurobehavioral function were founded among co-workers of the victims. This study showed that the methanol exposure under poor environmental control not only produce eye and CNS symptoms but also affect neurobehavioral function and optic nerve.

The term STODS (Surgical Temporary Ocular Discomfort Syndrome) has been coined to describe the ocular surface perturbations induced by surgery. As one of the most important refractive elements of the eye, Guided Ocular Surface and Lid Disease (GOLD) optimization is fundamental to success in achieving refractive outcomes and mitigating STODS. Effective GOLD optimization and the prevention/treatment of STODS, requires an understanding of the molecular, cellular and anatomic factors that influence ocular surface microenviroment and the associated perturbations induced by surgical intervention. By reviewing the current understanding of STODS etiologies, we will attempt to outline a rationale for a tailored GOLD optimization depending on the ocular surgical insult. With a bench to bedside approach, we will highlight clinical examples of effective GOLD perioperative optimization can mitigate STODS deleterious effect on preoperative imaging and postoperative healing.

Purpose: To investigate the effect of pigment dispersion on trabecular meshwork (TM) cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose, migrate, and contract were quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: TM cells readily phagocytosed pigment granules. Pigment induced stress fiber formation (pigment (P): 60.1 ± 0.3%, n = 10, control (C): 38.4 ± 2.5%, n = 11, P < 0.001) and contraction at 24 hours onward (P < 0.01). Phagocytosis declined (P: 68.7 ± 1.3%, C: 37.0 ± 1.1%, n = 3, P < 0.001) and migration was reduced after 6 hours (P: 28.0.1 ± 2.3, n = 12, C: 40.6 ± 3.3, n = 13, P < 0.01). Microarray analysis revealed that Rho, IGF-1, and TGFβ signaling cascades were central to these responses. Conclusions: TM cell exposure to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma.

Background: To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent onset non-arteritic anterior ischemic optic neuropathy (NAION). Method: Ninety-nine eyes of 99 patients diagnosed with NAION within 5 days of onset were included in this single masked randomized clinical trial. Thirty-four patients were randomized into group 1 (systemic erythropoietin), group 2 (oral steroids), and group 3 (control). Group A received 10,000 units of erythropoietin twice a day for three days. Group B received oral prednisone 75 mg daily for two weeks followed by a tapering dose (70 mg for 5 days, 60 mg for 5 days, and 5 mg reductions thereafter every 5 days). Functional and structural outcomes were analyzed at 3 and 6 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measure, and mean deviation (MD) of visual field (VF) test and peripapillary retinal nerve fiber layer thickness (PRNFLT) were secondary outcome measures. Results:The mean BCVA (±SD) at the time of presentation was 1 ± 0.56, 1.01 ± 0.6, and 0.94 ± 0.47 logMAR in groups A, B, and C, respectively (P = 0.140); corresponding values were 0.72 ± 0.45, 0.83 ± 0.46, and 0.78 ± 0.4 logMAR (P = 0.417), and at 6-month follow-up, they were 0.70 ± 0.44, 0.73 ± 0.35, and 0.75 ± 0.39 logMAR, respectively (P = 0.597). Fifty-five percent of patients in group A vesus 34.3% in group B, and 31.2% in group C had an improvement of at least 3 lines in the BCVA values at the 6th-month follow-up visit. (P= 0.04) The mean deviation (MD) at the time of presentation was 19.67 ± 6.2, 20.83 ± 4.83, and 18.94 ± 6.92 decibels (db), respectively (P= 0.483).The corresponding values at month 3 were 18.22 ± 7.5, 19.82 ± 7.15, and 17.65 ± 7.22 db, (P = 0.848); and at month 6 they were 16.56 ± 7.08, 18.15 ± 6.57, and 15.9 ± 5.97 db, respectively. (P = 0.699) PRNFLT at presentation was 189 ± 58, 193 ± 64, and 199 ± 62 micrometers, respectively (P = 0.779), which decreased to 110 ± 45, 127 ± 37, and 119 ± 37 at month 3 (P = 0.423). The corresponding values for month 6 were 88 ± 12, 74 ± 25, and 71 ± 18, respectively (P = 0.041). Conclusion: The findings of our study indicate the beneficial effects of systemic erythropoietin in preserving the function and structure of the optic nerve in recent onset NAION.

Glaucoma is a disease associated with retina of eye. Presently, millions of human being is suffering from this disease. Early detection of these diseases can save the people from blindness. Therefore, various methods have been developed for its detection. In this paper, we have studied the reported methods and summarized their performance in terms of accuracy of detection.

Mitochondrial dysfunction and oxidative stress are thought to be relevant to the pathogenesis of age-related macular degeneration (AMD). Glutathione (GSH) homeostasis fulfills a number of important roles in mitochondria, such as maintenance of mitochondrial DNA and respiratory competency of cells. Although the transport of mitochondrial GSH (mGSH) is not fully understood, increasing evidence from non-ocular tissues suggests that OGC (2-oxoglutarate carrier, SLC25A11) and DIC (dicarboxylate carrier, SLC25A10) are involved in mGSH transport. However, whether OGC and DIC mediate the transfer of GSH into the mitochondria of retinal pigment epithelial cells (RPE) remains unknown. Thus, we investigated the expression, localization, and function of OGC and DIC in human RPE (hRPE) in relation to oxidative stress and GSH. Both OGC and DIC are expressed in hRPE and are localized in mitochondria. We also found a dose and time-dependent decrease of OGC and DIC expression under oxidative stress and increased expression in polarized RPE. Our data show that the downregulation of OGC and DIC resulted in increased apoptosis and mGSH depletion which can be overcome by co-treatment with GSH-MEE. These findings suggest that overexpression of OGC and DIC may be an effective strategy to decrease susceptibility to mitochondrial toxicants by elevation of mGSH.

Purpose: To compare the efficacy and safety of graft-free short tunnel small flap (STSF) technique with that of scleral patch graft (SPG) in Ahmed glaucoma valve (AGV) implantation. Design: Randomized clinical trial. Participants: Eighty-eyes of eighty patients with medically uncontrolled glaucoma including 41 in STSF and 39 eyes in SPG. Methods: Patients were enrolled and assigned randomly to STSF or SPG. Main Outcome Measures: tube exposure, Intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), surgical complications, and success rate ( defined as intraocular pressure (IOP) >5 mmHg, ≤21 mmHg, and IOP reduction ≥20% from baseline at two consecutive visits after three months, no reoperation for glaucoma). Results: only one case in SPG developed tube exposure at 1-year follow-up. The cumulative probability of success during the first year of follow-up was 70% in the STSF and 65% in SPG (P = 0.36). IOP decreased significantly from 29.6 ± 8.6 mmHg at baseline to 16.4 ± 3.6 mmHg at the final follow-up in STSF (p = 0.001). The corresponding numbers for SPG were 30.9 ± 11.2 and 15.8 ± 4.7, respectively (p = 0.001). The final IOP was comparable between both groups (p = 0.65). Mean ± standard deviation of the number of glaucoma medications was 1.8 ± 0.9 in STSF and 1.6 ± 0.9 in SPG at final follow-up (P = 0.32). Postoperative complications developed in 8 patients (19%) in STSF and 9 patients (23%) in SPG (P = 0.81). Conclusions: STSF and SPG techniques had comparable complication rate at one-year follow-up. Both techniques were comparable in terms of success rate, postoperative IOP, and glaucoma medications.

Purpose: To investigate the relationship of lamina cribrosa displacement to corneal biomechanical properties and visual function after mitomycin C-augmented trabeculectomy. Method: Eighty-one primary open angle eyes were imaged before and after trabeculectomy using an enhanced depth spectral-domain optical coherence tomography (SDOCT). Corneal biomechanical properties were measured with the Ocular Response Analyser before the surgery. The anterior lamina cribrosa (LC) was marked at several points in each of six radial scans to evaluate LC displacement in response to Intraocular pressure (IOP) reduction. A Humphrey visual field test (HVF) was performed before the surgery as well as three and six months postoperatively. Results: Factors associated with a deeper baseline anterior lamina cribrosa depth (ALD) were cup-disc ratio (P=0.04), baseline IOP (P= 0.01), corneal hysteresis (P= 0.001), and corneal resistance factor (P= 0.001). After the surgery, the position of LC became more anterior (negative), posterior (positive) or remained unchanged. The mean LC displacement was -42 μm (P= 0.001) and was positively correlated with the magnitude of IOP reduction (regression coefficient: 0.251, P=0.02), and negatively correlated with age (regression coefficient: - 0.224, P= 0.04) as well as baseline cup-disk ratio (Regression coefficient: -0.212,P= 0.05) Eyes with a larger negative LC displacement were more likely to experience an HVF improvement of more than 3 dB gain in mean deviation (P= 0.002). Conclusion: A lower SDOCT cup-disc ratio, younger age, and a larger IOP reduction were correlated with a larger negative LC displacement and improving HVF. Corneal biomechanics did not predict LC displacement.

Purpose: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model. Methods: In perfused porcine anterior segments, 90 degrees of trabecular meshwork (TM) were ablated using the Trabectome (T; n = 8), Goniotome (G; n = 8), or Kahook device (K; n = 8). After 24 hours, additional 90 degrees of TM were removed. Intraocular pressure (IOP) and outflow facility were measured at 5 µL/min and 10 µL/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology. Results: At 5 µL/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P = 0.013). IOP reduction between G and K was similar (P = 0.420). Removing another 90 degrees of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µL/min compared with G and K (first ablation: 3.41 times increase versus 1.95 and 1.87; second ablation: 4.60 versus 2.50 and 1.74) with similar results at 10 µL/min (first ablation: 3.28 versus 2.29 and 1.90 (P = 0.001); second ablation: 4.10 versus 3.01 and 2.01 (P = 0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints. Conclusions: T, G and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.

Abstract: The aim of this study is to emphasize on the clinical uses of amniotic membrane (AM) in multiple ocular disorders. AM possesses many properties including promotion of epithelialization, anti-fibrotic, anti-apoptotic, anti-angiogenic properties. Epithelial wound healing on the eye surface is promoted due to several epidermal and keratocyte growth factors as well as by its anti-inflammatory and anti-scarring effects due to interleukin-10, interleukin-1 receptor antagonists and inhibition of transforming growth factor- beta (TGF-β) signal transduction by AM in the corneal and conjunctival fibroblasts respectively. It plays a crucial role by functioning as a substitute of basement membrane (BM) and as a temporary graft material. It is not only being used as an eye graft but also its extract can be used as an eye drop for corneal and external eye diseases. So its proper preparation, preservation and clinical application can bring a revolutionary change in the treatment of different ocular disorders.

The exact etiology of myopia remains elusive. The author proposes the particle property of photon in living tissue and the photon-electron theory in living tissue, if the frequency of the photon exceeds the threshold, the photon has enough energy to strike the electron away and forms a hole of a diameter in photon diameter scale in living tissue include the eye. Longer time of high-frequency electromagnetic radiation will cause more holes and a larger radius of holes. The visual light which passes through the radiated hole in the eye cannot be refracted on the macula, this is myopia symptom of blurred vision, shortening the distance of the eye and the object will include more visual light into cornea and lens, this is myopia another symptom of nearsightedness. The particle property of photon causes elongation of the eye and the macular holes.Blue light and X-ray are two kinds of high-frequency electromagnetic radiation which can shot holes in eye and cause myopia.

Preclinical animal studies provide valuable opportunities to better understand human diseases and contribute to major advances in medicine. This review provides a comprehensive overview of ocular parameters in humans and selected animals, with a focus on the ocular surface, detailing species differences in ocular surface anatomy, physiology, tear film dynamics and tear film composition. We describe major pitfalls that tremendously limit the translational potential of traditional laboratory animals (ie., rabbits, mice and rats) in ophthalmic research, and highlight the benefits of integrating companion dogs with clinical analogues to human diseases into preclinical pharmacology studies. This One Health approach can help accelerate and improve the framework in which ophthalmic research is translated to the human clinic. Studies can be conducted in canine subjects with naturally occurring or non-invasively induced ocular surface disorders (eg., dry eye disease, conjunctivitis), reviewed herein, and tear fluid can be easily retrieved from canine eyes for various bioanalytical purposes. In this review, we discuss common tear collection methods, including capillary tubes and Schirmer tear strips, and provide guidelines for tear sampling and extraction to improve the reliability of analyte quantification (drugs, proteins, others).

We studied short- and long-term effects of intravitreal injection of N-methyl-D-aspartate (NMDA) on melanopsin-containing (m⁺) and non-melanopsin-containing (Brn3a⁺) retinal ganglion cells (RGCs). In adult SD-rats, the left eye received a single intravitreal injection of 5µL of 100nM NMDA. At 3 and 15 months, retinal thickness was measured in vivo using SD-OCT. Ex vivo analyses were done at 3, 7, 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for Brn3a and melanopsin, the total number of Brn3a⁺RGCs and m⁺RGCs were quantified and their topography represented. In control retinas, the mean total numbers of Brn3a⁺RGCs and m⁺RGCs were 78,903±3,572 and 2,358±144 (mean ± SD; n=10), respectively. In the NMDA injected retinas, Brn3a⁺RGCs numbers diminished to 50% and 25%, at 3 and 14 days, respectively, but there was no further loss up to 15 months. The number of immunoidentified m⁺RGCs decreased significantly at 3 days, recovered between 3-7 days and was back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induce a rapid loss of 75% of Brn3a⁺RGCs, a transient downregulation of melanopsin expression but not m⁺RGC death, and a thinning of the inner retinal layers.

Diabetic retinopathy is the most common microvascular complication of diabetes mellitus and one of the leading causes of blindness globally. Due to the progressive nature of the disease, earlier detection and timely treatment can lead to substantial reductions in the incidence of irreversible vision-loss. Artificial intelligence (AI) screening systems have offered clinically acceptable and quicker results in detecting diabetic retinopathy from retinal fundus and optical coherence tomography (OCT) images. Thus, this systematic review and meta-analysis of relevant investigations was performed to document the performance of AI screening systems that were applied to fundus and OCT images of patients from diverse geographic locations including North America, Europe, Africa, Asia, and Australia. A systematic literature search on Medline, Global Health, and PubMed was performed and studies published between October 2015 and January 2020 were included. The search strategy was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, and AI-based investigations were mandatory for studies inclusion. The abstracts, titles, and full-texts of potentially eligible studies were screened against inclusion and exclusion criteria. Twenty-one studies were included in this systematic review; 18 met inclusion criteria for the meta-analysis. The pooled sensitivity of the evaluated AI screening systems in detecting diabetic retinopathy was 0.93 (95% CI: 0.92-0.94) and the specificity was 0.88 (95% CI: 0.86-0.89). The included studies detailed training and external validation datasets, criteria for diabetic retinopathy case ascertainment, imaging modalities, DR-grading scales, and compared AI results to those of human graders (e.g., ophthalmologists, retinal specialists, trained nurses, and other healthcare providers) as a reference standard. The findings of this study showed that the majority AI screening systems demonstrated clinically acceptable levels of sensitivity and specificity for detecting referable diabetic retinopathy from retinal fundus and OCT photographs. Further improvement depends on the continual development of novel algorithms with large and gradable sets of images for training and validation. If cost-effectiveness ratios can be optimized, AI can become a financially sustainable and clinically effective intervention that can be incorporated into the healthcare systems of low-to-middle income countries (LMICs) and geographically remote locations. Combining screening technologies with treatment interventions such as anti-VEGF therapy, acellular capillary laser treatment, and vitreoretinal surgery can lead to substantial reductions in the incidence of irreversible vision-loss due to proliferative diabetic retinopathy.

The purpose of this study is to assess the concentration-response relations between conjunctivitis and exposure to ambient ozone. This retrospective study includes emergency department (ED) visits for conjunctivitis in Edmonton, Canada, for the period April 1992–March 2002. Daily average levels of ozone (range: 1.2–50.9, ppb), of temperature, and of relative humidity were estimated and used for the period of the study. For each of the considered exposure lags, (from 0 to 9 days), six different models were fitted to estimate the concentration-response function. The goodness of fit was assessed using the Akaike information criterion. During the period of the study, 17,211 ED visits for conjunctivitis were recorded and used. For all subjects together, a positive statistically significant association was obtained for the exposure lagged by 5 days. For female subjects, lags 1, 3, and 9 had positive statistically significant associations (lag 2 had negative associations). For male subjects, only lag 5 had a positive statistically significant association. The estimated non-linear concentration-response functions for the considered groups (all, males, females) and lags, revealed the associations along the exposure levels. The fitted shapes are described by algebraic functions and may have various forms. The estimated functions are useful to determine the risk associated with exposure to ground-level ozone.

1) Background: CFH and HTRA1 genes are traditional markers of increased risk of AMD across populations. Recent findings suggest that additional genes, for instance, in the dystrophin-associated protein complex might be promising markers for AMD. 2) Methods: Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of 134 cases with 134 unpaired controls. Cases were 60 years or older (CARMS grade 4-5, as assessed by experienced ophthalmologists following the AAO guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or RPE changes on fundus exam and negative family history of AMD. We examined SNPs in the SGCD gene: rs931798, rs140617, rs140616, and rs970476 by sequencing and RT-PCR. Genotyping quality check and univariate analyses were performed with PLINK v.1.9. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. 3) Results: After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% (1.81, 95%CI 1.06-3.14, p=0.031), especially the geographic atrophy phenotype (1.82, 95%CI 1.03-3.21, p=0.038) compared to the G/G homozygous. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (Adjusted OR 0.13, 95%CI 0.02-0.91, p=0.041). 4) Conclusions: SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted.

In mice, mutations or targeted disruptions of the core circadian gene Bmal1 have been implicated in early onset of ocular pathologies, including premature/congenital cataract development. The aim of the present study was to analyze probands of consanguineous Pakistani cataract families to identify the novel pathogenic variants in the BMAL1 gene. We have studied 21 congenital cataract families. Ophthalmic examination was performed for the probands and available family members. Genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing was performed for the entire coding region of the BMAL1 gene. Targeted Sanger sequencing of BMAL1 revealed a heterozygous variant c.41A>T; p.(Asp14Val) in one proband, but it did not co-segregate with the disease phenotype in the family. In addition, a nonsynonymous variant (rs2290037) was identified in five probands. Our study is the first one to analyze the role of BMAL1 gene mutations in humans for their association with congenital cataract. Although we were unable to find the variants associated with congenital cataract families from Pakistan, more studies from other populations will be informative to further prove the role of BMAL1 with the disease.

Voltage-gated Ca²⁺ (Ca_v) channels play pivotal roles in regulating gene transcription, neuronal excitability, and neurotransmitter release. In order to meet the spatial and temporal demands of visual signaling, Ca_v channels exhibit unusual properties in the retina compared to their counterparts in other areas of the nervous system. Here, we review current concepts regarding the specific subtypes of Ca_v channels expressed in the retina, their intrinsic properties and forms of modulation, and how their dysregulation could lead to retinal disease.

Aim: Reporting 3 year outcomes of a community shared care scheme run by specialised independent prescribing (IP) optometrists for stable glaucoma and ocular hypertension (OHT) patients in West Kent, England. Purpose: Shared Care Schemes for glaucoma exist to alleviate the burden on Hospital Eye Services (HES) glaucoma clinics. We studied the effectiveness of community care by highly trained and qualified IP optometrists in terms of disease stability and referral rate into HES.Methods: Retrospective longitudinal review of 200 eyes with stable early to moderate stage glaucoma and OHT followed-up in two specialist optometry practices. Outcome measures included visual field mean deviation (VFMD), intraocular pressure (IOP), changes to treatment and referral rate into HES. Inclusion criteria included all patients with OHT and glaucoma (open angle and primary angle closure) referred for community follow-up. Incomplete data sets were excluded.Results: Mean age 71yrs (range 28 - 93yrs) and equal male: female ratio. n= 159 at year 3. The results for both outcomes showed no significant change from baseline at 12 or 24-month time points. However, a significant change from baseline at 36 months was observed for both outcomes: mean reduction of 0.7 mmHg in IOP, and a mean reduction of 0.3 dB in VFMD. There was a statistically significant change in the number of drops used at 36 months (p=0.001). 11 patients had a change in medication within 3 years. One patient was referred back to HES for uncontrolled IOP and consideration of trabeculectomy.Conclusion: Community follow-up of stable cases of glaucoma and OHT by highly qualified IP optometrists was safe, with stability of disease maintained and few referrals back to HES.

Marfan syndrome is an autosomal dominant genetic connective tissue disorder that results from mutations in the fibrillin-1 gene located on chromosome band 15q 15–21. Fibrillin, a glycoprotein, is widely expressed throughout the body and contribute to elasticity and force-bearing capacity of connective tissue. In the eye, fibrillin is a key constituent of the ciliary zonules, which suspend the crystalline lens in place. The zonular defect leads to ectopia lentis that is hallmark of Marfan ocular abnormalities and occurs in 60 to 80% of cases. Other less common ocular features of Marfan syndrome are increased axial length, astigmatism, and flat cornea. Visual function in Marfan syndrome could be affected in several ways: ectopia lentis, refractive error, amblyopia, retinal detachment, cataract, and glaucoma. Management of subluxated lens starts with correction of refractive error with eyeglasses in mild cases. In more severe cases, especially when lens bisects the pupil, complete correction of refractive error is impossible without removing subluxated lens. The best method for visual rehabilitation after lens extraction is still debated. Aphakic Artisan implantation at the time of subluxated lens removal results in good visual outcomes with acceptable safety profile. Studies with longer term follow up and larger sample populations are needed to evaluate the safety of this procedure in patients with Marfan syndrome.

Uveal melanoma is the most common primary intraocular malignancy in adults characterized by insidious onset and poor prognosis strongly associated with tumor size and the presence of distant metastases, most commonly in the liver. Contrary to most tumor identification, biopsy followed by pathological exam is not recommended in ophthalmic oncology. Therefore, early and non-invasive diagnosis is essential to enhance patients’ chances for early treatment possibilities. We reviewed imaging modalities currently used in the diagnosis of uveal melanoma, i.e., fundus imaging, ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF). The principle of imaging techniques was briefly explained, along with their role in the diagnostic process and a summary of their advantages and limitations. Further, the experimental data and the advancements in imaging modalities were searched. We described their innovations, showed current usage and research, and explained the possibilities of utilizing them to diagnose uveal melanoma and their potential application in personalized medicine such as theranostics.

Purpose: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. Methods: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, an additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. Results: After the first 90° TM excision, IOP was significantly lower in G (10.23±2.39 mmHg, n=7) than C (20.04±1.97mmHg, n=8, P<0.01). Outflow facility in G (0.38±0.07 µl/min/mmHg) was higher than C (0.16±0.02 µl/min/mmHg, P<0.01). After the second 90° TM excision, IOP in G (6.46±0.81 mmHg, n=7) was significantly lower than C (20.25±1.66 mmHg, n=8, P<0.001), while the outflow facility in G (0.50±0.05 µl/min/mmHg, n=7) was higher than C (0.16±0.01 µl/min/mmHg, n=8, P<0.001). Compared to the first excision, excision of an additional 90° did not change of IOP (P=0.20) or outflow facility (P=0.17) further. Conclusion: Excision of 90° of TM in a pigmentary glaucoma model using an aspirating dual-blade decreased IOP and increased outflow facility. Translational Relevance: Microsurgical TM excision over 90° can effectively restore outflow in pigmentary glaucoma.

Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.

Glucosamine is the most common nutrition supplement used in the United States. It is promoted not only as a pain reliever but also a therapy to slow osteoarthritis. Although studies with 3,800 patients with osteoarthritis of the knee or hip found that glucosamine was no better than placebo, it continues to be used for these two indications due to its perceived safety. However, reports of an increased intraocular pressure are alarming, especially in glaucoma. Glycosaminoglycans play a key role in the physiology of the cornea, conventional outflow of aqueous humor and the retina. In theory, long-term treatment with glucosamine could reach a concentration that impacts the morphology and function of ocular tissues. We recommend ophthalmologists counsel glaucoma patients about the potential risks of glucosamine and encourage cessation in uncontrolled intraocular pressure.

(1) Background: drugs provide a significant benefit; however, their use implies an intrinsic potential danger, with the possibility to cause unwanted effects. These effects are known as adverse drug reactions (ADRs). Post-marketing drug safety surveillance detects unknown risks that have not been identified in clinical trials and it is necessary to monitor marketed medications under real-life practice. Due to the scarce information about fixed combination of ciprofloxacin 0.3% / dexamethasone 0.1% (SDO), we performed a drug safety surveillance study. (2) Methods: A prospective non-controlled drug safety surveillance study was conducted in Peruvian population. A total of 236 patients prescribed SDO were included derivates from 12 sites. Patients' standardized information was collected through two phone calls, including demographics, medical history, prescribing patterns of SDO, concomitant medication, and ADRs in detail. The ADRs were classified by causality and severity, followed by outcome measures to identify new risk. (3) Results: 236 patients prescribed with SDO participated in the study and 220 were included. A total of 82 ADRs/220 patients were reported after the use of SDO, presenting a ratio 0.37 ADR/patient. The most frequent ADR with SDO administration was eye irritation (30%). The totality of the ADR was classified as non-serious, and the 97.5% (n=80) was classified as mild and 2.5% as moderate (n=2). No cases under the severe category were identified. (4) Conclusion: No new risks were found in the population where this study was conducted.

Purpose: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. Methods: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 10⁷ pigment particles/mL for 48 hours before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated. Result: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed. Conclusion: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load.

Cornea severe inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. The cornea can be used to study the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, Methanol (Met) and Hexane (Hex), from the seed of Cucurbita argyrosperma, in the inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. Clinical manifestation as opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological evaluation were performed. Inflammatory (COX-2, NF-κB, and IL-1β), and angiogenic (VEGF-A, VEGFR1, VEGFR2) markers were assessed by immunohistochemistry. Cox-2, Il-1β, and Vegf-a mRNA levels were also determined. After treatments, we observed slim corneal thickness with lower opacity scores and low cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased CNV area. The staining of inflammatory and angiogenic factors was significantly decreased. These effects are related to a down-expression of Cox-2, Il-1β, and Vegf. These results suggest that intake of C. argyrosperma seed can be used to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.

Purpose: To determine whether 24-hour IOP monitoring can be a predictor for glaucoma progression and to analyze the inter-eye relationship of IOP, perfusion and progression parameters. Methods: We extracted data from manually drawn IOP curves with HIOP-Reader, a software suite we developed. The relationship between measured IOPs and mean ocular perfusion pressures (MOPP) to retinal nerve fiber layer (RNFL) thickness was analyzed. We determined the ROC curves for peak IOP (Tmax), average IOP (Tavg), IOP variation (IOPvar) and historical IOP cut-off levels to detect glaucoma progression (rate of RNFL loss). Bivariate analysis was conducted to check for various inter-eye relationships. Results: 217 eyes were included. The average IOP was 14.8±3.5 mmHg, with a 24-hour variation of 5.2±2.9 mmHg. 52% of eyes with RNFL data showed disease progression. There was no significant difference in Tmax, Tavg and IOPvar between progressors and non-progressors (all p>0.05). Except for Tavg and the temporal RNFL, there was no correlation between disease progression in any quadrant, Tmax, Tavg and IOPvar. 24-hour and outpatient IOP variables had poor sensitivities and specificities in detecting disease progression. The correlation of inter-eye parameters was moderate; correlation with disease progression was weak. Conclusion: In line with our previous study, IOP data obtained during a single visit (outpatient or inpatient monitoring) make for a poor diagnostic tool, no matter the method deployed. Glaucoma progression and perfusion pressure in left and right eyes correlated weakly to moderately with each other.

Purpose: To investigate the extent of anterior chamber angle circumference needed to maintain a physiological outflow facility (C). Methods: Twenty anterior segments of porcine eyes were assigned to 5 groups, each with a different degree of cyanoacrylate-mediated angle closure: 90° (n = 4), 180° (n = 4), 270° (n = 4), 360° (n = 4) and four unoccluded control eyes. The outflow facility was measured at baseline, 3, 12, 24, and 36 hours after angle closure. Outflow patterns were evaluated with canalograms and the histomorphology was compared. Results: Baseline outflow facilities of the five groups were similar (F = 0.922, P = 0.477). Complete, circumferential occlusion over 360° induced a significant decrease in facility from baseline at all time-points (P ≤ 0.023 at 3, 12, 24 and 36 hours). However, no difference from baseline was found in any of the partially-occluded (0–270°) groups (F ≥ 0.067, P ≥ 0.296 at 3, 12, 24 and 36 hours). The canalograms confirmed the extent of occlusion with flow through the unblocked regions. Histology revealed no adverse effects of blockage on the TM or aqueous plexus in the unoccluded angle portions. The unoccluded TM appeared normal. Conclusion: Cyanoacrylate-mediated angle occlusion created a reproducible angle closure model. 90° of unoccluded anterior chamber angle circumference was sufficient to maintain physiological outflow. This model may help understand how outflow can be regulated in healthy, nonglaucomatous TM.

Background: The assessment of the incidence and characteristic of acute and chronic post-operative endophthalmitis (POE) after cataract surgery in Poland during 2010 - 2015. Patients and methods: All hospitalizations of patients, in the National Database of Hospitalizations, who underwent cataract surgery alone or in combined procedures in Poland between January 2010 and December 2015, with a billing code of endophthalmitis, were selected. Acute endophthalmitis was identified if symptoms occurred within 1 - 42 days from the cataract surgery and chronic endophthalmitis if symptoms occurred ≥ 43 days after cataract surgery, respectively. Results: In total, 1331 cases of POE after 1,218,777 cataract extractions were identified. The overall incidence of POE decreased from 0.125% in 2010 to 0.066% in 2015. In multiple logistic regression analyses, increasing age was significantly associated with acute POE, while type II diabetes mellitus, extracapsular cataract extraction and one-day surgery were significantly associated with chronic POE. The combined cataract surgery and male sex were significant risk factors for both acute and chronic POE. A total of 62.51% of all eyes affected by POE received antibiotic treatment and 37.49% had vitrectomy treatment. Conclusions: During the study period, the total incidence of post-operative endophthalmitis after cataract surgery decreased significantly.

A better study of the postnatal retinal development is not only essential for the in-depth understanding of the nature of the vision system but also may provide insights for treatment developments of eye conditions, such as retinopathy of premature (ROP). To date, quantitative analysis of postnatal retinal development is primarily limited to endpoint histological examination. This study is to validate in vivo optical coherence tomography (OCT) for longitudinal monitoring of postnatal retinal development in developing mouse eyes. Three-dimensional (3D) frame registration and super averaging were adopted to investigate the fine structure of the retina. Interestingly, a hyporeflective layer (HRL) between the nerve fiber layer (NFL) and inner plexiform layer (IPL) was observed in developing eyes and gradually disappeared with aging. To interpret the observed retinal layer kinetics, a model based on eyeball expansion, cell apoptosis, and retinal structural modification was proposed.

There is a lack of research based on in-depth theoretical and scientific knowledge to understand the visually impaired, and there has been little effort in the application of strategies for early intervention to minimize risk these people might encounter during development.. This study used semi-structured interviews from eight persons with visual impairments who had various experiences with resiliency. Three resilience processes based on life experiences were identified: 1) Experience and Adaptation: “self-awareness of disability” and “adaptation disability and the environment”; 2) Facing the Circumstances: “the exposure to concealment and abuse,” “the suppression of potential,” “denial and abandonment by family,” “poverty and disability,” “exchange and self-regulation,” and “social integration” themes; and 3) the Positive Reinforcement: “self-disclosure and jump-starting life,” “maintenance of a positive thinking,” and “socioeconomic independence.” These findings expand the understanding of the factors common to the resilience process experienced by individuals with visual impairment and highlight the importance of psychological support, family, education, and social support.

Machine learning (ML) has a large capacity to learn and analyze a large volume of data. This study aimed to train different algorithms to discriminate between healthy and pathologic corneal images by evaluating digitally processed spectral-domain optical coherence tomography (SD-OCT) corneal images. A set of 22 SD-OCT images belonging to a random set of corneal pathologies was compared to 71 healthy corneas (control group). A binary classification method was applied; three approaches of ML were used. Once all images were analyzed, representative areas from every digital image were also processed and analyzed for a statistical feature comparison between healthy and pathologic corneas. The best performance was obtained from transfer learning - support vector machine (TL-SVM) (AUROC = 0.94, SPE 88%, SEN 100%) and transfer learning – random forest (TL- RF) method (AUROC = 0.92, SPE 84%, SEN 100%), followed by convolutional neural network (CNN) (AUROC = 0.84, SPE 77%, SEN 91%) and random forest (AUROC = 0.77, SPE 60%, SEN 95%). The highest diagnostic accuracy in classifying corneal images was achieved with the TL-SVM and the TL-RF models. In image classification, CNN was a strong predictor. This pilot experimental study developed a systematic mechanized system to discern pathologic from healthy corneas.

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter that is responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the co-effects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of the mouse retina. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same condition to 8–12 wk (young) or 45–55 wk (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to that from aged WT mice, and subsequence gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision, and transcellular barrier function that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the 4 age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.

The electrical stimulation of the visual cortices has the potential to restore vision to blind individuals. Until now, the results of visual cortical prosthetics has been limited as no prosthesis has restored a full working vision but the field has shown a renewed interest these last years thanks to wireless and technological advances. However, several scientific and technical challenges are still open in order to achieve the therapeutic benefit expected by these new devices. One of the main challenges is the electrical stimulation of the brain itself. In this review, we analyze the results in electrode-based visual cortical prosthetics from the electrical point of view. We first briefly describe what is known about the electrode-tissue interface and safety of electrical stimulation. Then we focus on the psychophysics of prosthetic vision and the state-of-the-art on the interplay between the electrical stimulation of the visual cortex and phosphene perception. Lastly, we discuss the challenges and perspectives of visual cortex electrical stimulation and electrode array design to develop the new generation implantable cortical visual prostheses.

Purpose: To compare ab interno trabeculectomy by trabecular meshwork excision to plasma-mediated ablation in primary open-angle glaucoma. Methods: Retrospectively collected data of TrabEx+ (TEx, n=56) and Trabectome (T, n=99) were compared by coarsened exact matching to reduce confounding and matched based on baseline IOP and age. Primary outcomes were IOP and number of glaucoma medications. Complications and need for additional glaucoma surgery were assessed. Patients were followed for up to one year. Results: 53 TEx could be matched to T. Baseline IOP was 16.5±4.6 mmHg in both; age was 73.7±8.8 and 71.5±9.9 years in TEx and T, respectively. TEx were taking more medications than T (p<0.001). IOP was reduced to 14.8±4.3 in TEx and to 13.4±3.4 in T at 6 months, and to 14.9±6.0 (p=0.13) in TEx and to 14.1±3.8 mmHg (all p<0.05) in T at 12 months. Medications were reduced at both 6 and 12 months (p< 0.05). No differences were seen between TEx and T at 6 and 12 months. In TEx, only one serious complication occurred, and two patients required further glaucoma surgery. Conclusion: Although both groups had a baseline IOP considered low for ab-interno trabeculectomy, IOP and medications were reduced further at 6 and 12 months. IOP reduction did not reach significance in TEx at 12 months. The inter-group comparison did not reveal any significant differences. Both had a low complication rate.

Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.

This study compares the efficacy of the two most commonly used surgical methods for pterygium in the Polish population, conjunctival autograft versus amniotic membrane transplantation, and to evaluate the postopera-tive recurrence rate. We retrospectively analysed the medical records of 65 patients who underwent surgery for primary or recurrent pterygium at an ophthalmology clinic in Bialystok, Poland between 2016 and 2020. Surgical success (no regrowth) occurred in almost half of the amniotic membrane patients (44%) and in most of the conjunctival autograft patients (79%); this was a significant relationship. The odds of successful surgery were 79% lower for subjects with amniotic membranes than for those with conjunc-tival autografts (OR with 95% CI = 0.21 (0.05; 0.94]; p = 0.045). Our study confirms that in Polish Caucasian population the success rate of the pro-cedure using conjunctival autograft versus the use of amniotic membrane, is in favoured for the procedure with conjunctival graft.

Purpose: Nycthemeral (24-hour) glaucoma inpatient intraocular pressure (IOP) monitoring has been used in Europe for more than 100 years to detect peaks missed during regular office hours. Data supporting this practice is lacking, partially because it is difficult to correlate manually drawn IOP curves to objective glaucoma progression. To address this, we deployed automated IOP data extraction tools and tested for a correlation to a progressive retinal nerve fiber layer loss on spectral-domain optical coherence tomography (SDOCT). Methods: We created and deployed a machine-learning image analysis software to extract IOP data from hand-drawn, nycthemeral IOP curves of 225 retrospectively identified glaucoma patients. The relationship between demographic parameters, IOP and mean ocular perfusion pressure (MOPP) data to SDOCT data was analyzed. Sensitivities and specificities for the historical cut-off values of 15 mmHg and 22 mmHg in detecting glaucoma progression were calculated. Results: IOP data could be extracted efficiently. The IOP average was 15.2±4.0 mmHg, nycthemeral IOP variation was 6.9±4.2 mmHg, and MOPP was 59.1±8.9 mmHg. Peak IOP occurred at 10 AM and trough at 9 PM. Disease progression occurred mainly in the temporal-superior and -inferior SDOCT sectors. No correlation could be established between demographic, IOP, or MOPP parameters and SDOCT disease progression. The sensitivity and specificity of both cut-off points (15 and 22 mmHg) were insufficient to be clinically useful. Outpatient IOPs were non-inferior to nycthemeral IOPs. Conclusion: IOP data obtained during a single visit make for a poor diagnostic tool, no matter whether obtained using nycthemeral measurements or during outpatient hours.

In the last few decades, glaucoma became the second biggest leading cause of irreversible vision loss. Because of its asymptotic growth, it is not properly diagnosed until the relatively late stage. To stop the severe damage by glaucoma it is needed to detect glaucoma in its early stages. Surprisingly diabetes also be the greatest cause of glaucoma. In the modern era, artificial intelligence makes great progress in the medical image processing field. Image analysis based on machine learning gives a huge success in diagnosis glaucoma without any misdiagnosis. The aim of this proposed paper is to create an automated process that can detect glaucoma and diabetic retinopathy. Here various Machine Learning models are used and results of these methods are presented.

Importance: Because of the high prevalence of myopia in Taiwan, understanding the risk factors for its development and progression is important to public health. Background: This study investigated the risk factors for myopia and their influence on the progression of myopia in schoolchildren in Taiwan. Design: Patients’ clinical records were obtained retrospectively from ophthalmologists. Questionnaires were given to collect demographic information, family background, hours spent on daily activities, myopia progression, and treatment methods. Participants: A total of 522 schoolchildren with myopia from a regional medical hospital in northern Taiwan participated the study. Written informed consent was obtained from the participants of legal age or the parents or legal guardians. Methods: Multivariable regression analyses were performed. Myopia measured in dioptres was analysed, controlling for patients’ family and demographic information as well as their daily behaviours. Main Outcome Results: Children with high myopic parents were more myopic. Earlier onset age of myopia was associated with a higher level of myopia and greater annual myopic progression. Children reporting more near work activities had higher levels of myopia and greater progression of myopia. Lower levels of myopia were associated with more exercise, longer periods of sleep, and better vision care knowledge in children and parents. Intake of food supplements had no effect on myopia. Conclusions and Relevance: In addition to genetics, education, environment, and near work activity can influence the development of myopia. Health policies for schoolchildren should promote protective activities and vision care knowledge in order to protect the eyesight of schoolchildren.

Purpose: To investigate the molecular basis of congenital glaucoma in a family with GAPO (growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy) syndrome. Methods: We report ocular features of 3 girls with GAPO syndrome born of consanguineous marriage in a multi- generation consanguineous family. The proband (4year old girl) and her younger sibling (1 year old girl) were operated for bilateral congenital glaucoma in both eyes. The elder sibling (10year old female) had features of GAPO syndrome but did not manifest features of glaucoma. Results: A genetic evaluation using whole exome sequencing revealed a homozygous ANTXR1 mutation in all 3 affected siblings with GAPO. No other mutations were detected in the genes associated with glaucoma. A rare missense mutation in TGFBI gene was shared in the two siblings with congenital glaucoma and GAPO syndrome.Conclusions: Mutations in TGFBI gene could have a role in the pathogenesis of congenital glaucoma.

Good eyesight belongs to the most-valued attributes of health, and diseases of the eye are a significant health care burden. Case numbers are expected to further increase in the next decades due to an aging society. The development of drugs in ophthalmology, however, is difficult due to limited accessibility of the eye, in terms of drug administration and in terms of sampling of tissues for drug pharmacokinetics (PK) and pharmacodynamics (PD). Ocular quantitative systems pharmacology (QSP) models provide the opportunity to describe the distribution of drugs in the eye as well as the resulting drug-response in specific segments of the eye. In particular, ocular physiologically-based pharmacokinetic (PBPK) models are necessary to describe drug concentration levels in different regions of the eye. Further, ocular effect models employing molecular data from specific cellular systems are needed to develop dose-response correlations. We here describe the current status of PK/PBPK as well as PD models for the eye and describe cellular systems, data repositories as well as animal models in ophthalmology. The application of the various concepts is highlighted for the development of new treatments for post-operative fibrosis after glaucoma surgery.

Neovascular age-related macular degeneration (nAMD) accounts for one of the leading causes of blindness among the aging population. The current treatment options for nAMD include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). However, standardised frequent administration of anti-VEGF injections only improves the vision in approximately 30%-40% of nAMD patients. Current therapies targeting nAMD pose a significant risk of retinal fibrosis and geographic atrophy (GA) development in nAMD patients. A need exists to develop new therapies to treat nAMD with effective and long-term anti-angiogenic effects. Recent research on nAMD has discovered novel therapeutic targets and angiogenic signalling mechanisms involved in its pathogenesis. For example, tissue factor, human intravenous immune globulin, interferon-β signalling, cyclooxygenase-2 (COX-2) and cytochrome P450 monooxygenase lipid metabolites have been identified as key players in the development of angiogenesis in AMD disease models. Furthermore, novel therapies such as NLRP3 inflammasome inhibition, targeted intraceptor nanoparticle therapy, inhibitors of integrins and tissue factor are currently being tested at the level of clinical trials to treat nAMD. The aim of this review is to discuss the scope for alternative therapies proposed to anti-VEGFs for the treatment of nAMD.

Purpose: To investigate trabeculopuncture (TP) for predicting the outcome of ab interno trabeculectomy (AIT). AIT is an effective, low-risk procedure for open angle glaucoma. Despite widespread utilization, it fails in patients with an unidentified distal outflow resistance. Methods: We bisected 81 enucleated porcine eyes and perfused them for 72 hours. They were assigned to two groups: trial (n=42) and control (n=39). Intraocular pressure (IOP) was measured continuously. At 24 hours, four YAG-laser trabeculopunctures on the nasal trabecular meshwork were performed, followed by a 180° AIT at the same site at 48 hours. Eyes were divided into TP and AIT responders and non-responders; the proportion of TP responders between both AIT groups was compared. Results: Both post-TP and post-AIT IOPs were lower than baseline IOP (p=0.015 and p<0.01, respectively). The success rates of TP and AIT were 69% and 85.7%, respectively. The proportion of TP responders among AIT responders was greater than that of AIT non-responders (p<0.01). Sensitivity and specificity values of TP as predictive test for AIT success were 77.7% and 83.3%, respectively. The positive and negative predictive values were 96.6% and 38.5%, respectively. Conclusion: A 10% reduction in IOP after TP can be used as predictor for the success (>20% IOP decrease) of 180° AIT in porcine eyes.

Purpose: To compare the standard implantation technique of a new ab externo microshunt (PRESERFLO) to a posterior technique with a small incision. The standard anterior approach (A) requires a relatively large, 6-8 mm perilimbal peritomy. In contrast, the posterior approach (P) involves only a 2-3 mm snip incision 2 mm posterior to the limbus. Methods: Charts of 126 PRESERFLO patients (54 A and 72 P) were retrospectively analyzed. Follow-up was 270 days. We compared the surgical time, intraocular pressure (IOP), number of medications, and complications. Results: The preoperative IOP in A was 21.8±8.5 mmHg and 23.9±8.1 mmHg in P (p=0.08). The surgical time for A was 26±0.8 minutes and 10±0.4 minutes for B (p<0.001). Following a low-pressure phase during the first week, A and P had an IOP value of 10.8±5.9 mmHg and 10.6±4.5 mmHg at 30 days, respectively (p=0.62). IOPs remained at this level throughout the study (all intra-group p> 0.08). There were no inter-group differences in IOP at any visit (all p-values > 0.3). Patients in A and P took 3.2 ± 1.3 and 3.3 ± 1.0 pressure-lowering medications at baseline, respectively (p=0.4). These values declined to 0.2 ± 0.6 in A and 0.3 ± 0.7 in P at 270 days. Both groups had a similar number of revisions (13 (10.3%) versus 10 (7.9%, p=0.14)) and complications (26 (20.8%) versus 31 (24.6%, all p>0.25). Conclusion: The posterior PRESERFLO insertion technique was 2.6 times faster than the standard anterior technique and yielded similar results with a large reduction in IOP and medications and a safety profile favorable over traditional filtering surgery.

Refractive surgery is an increasingly popular procedure to decrease spectacle or contact lens dependency. The two most commonly used surgical techniques to correct myopia is Photorefractive keratectomy (PRK) and Femtosecond- Lasik (FS-LASIK)There are few publications that gathers such a long term follow up of both surgical techniques (2) Methods It has been performed a retrospective non-randomized study 509 PRK eyes and 310 FS-LASIK surgeries were followed for 10 years for the treatment of myopia and compound myopic astigmatism. Patients were followed up three months, one year, 2 years, 5 and 10 years. The safety index of both procedures was defined as a quotient between the postoperative BCVA (Best Corrected Visual Acuity) and the preoperative BCVA. The predictability is calculated as difference between the expected spherical equivalent and the achieved spherical equivalent. The efficacy index was calculated as a quotient between postoperative UCVA divided by the preoperative BCVA (3) Results. The results were: a safety index higher than 100% (109%) and an efficacy index of 82.4% after 10 years of PRK surgery in both groups. FS-LASIK was the safest surgery after 10 years and the most efficacy technique although in this case there were no statistically significant differences (4) Conclusions. All these data demonstrated better indexes for FS-LASIK

Purpose: To evaluate the efficacy and survival rates of trabectome-mediated ab interno trabeculectomy combined with non-fenestrated Baerveldt glaucoma implants (BT) in comparison to Baerveldt glaucoma implant alone (B).Method: A total of 175 eyes undergoing primary glaucoma surgery (60 eyes BT and 115 B) were enrolled in this retrospective comparative case series. Participants were identified using the procedural terminology codes. Groups were then matched using Coarsened Exact Matching (51 eyes in each group). The primary outcome measure was surgical success, defined as 5 mmHg < IOP ≤ 21 mmHg, and IOP reduction ≥ 20% from baseline, and no reoperation for glaucoma. Secondary outcome measures were intraocular pressure, the number of glaucoma medications, and best corrected visual acuity (BCVA).Results: The cumulative probability of success at one year was 61% in BT, and 50% in B. IOP decreased significantly from 23.5±2.4 mmHg at baseline to 14.1±2.7 mmHg at the final follow up in BT (P= 0.001). The corresponding numbers for B were 23.2± 2.0 and 13.9± 1.6, respectively (P= 0.001). There was no significant difference in IOP at the final follow-up (P=0.56). The number of medications at baseline was 2.3±0.3 in both groups. However, BT needed significantly fewer drops at all postoperative time intervals and used 1.1±0.3 (BT) and 2.0±0.4 eye drops (B) at the final follow-up visit (P= 0.004). No dangerous hypotony or hypertension occurred in BT.Conclusion: Similar rates of success and IOP reduction were observed in BT and B. BT needed significantly fewer glaucoma medications. Tube fenestration was not necessary in BT resulting in less postoperative hypotony and hypertension.

Purpose: To evaluate clinical outcomes after bilateral mix-and-match cataract surgery using extended depth of focus (EDOF) and diffractive multifocal (DMF) intraocular lenses (IOLs). Methods: Thirty-seven patients received Tecnis Symfony EDOF IOL (ZXR00) implantation in the dominant eye, and Tecnis +3.25 DMF IOL (ZLB00) in the non-dominant eye. Patients were followed for 3 months, and uncorrected and corrected distance visual acuity (UDVA, CDVA) , uncorrected intermediate and near visual acuity (UIVA, UNVA), contrast sensitivity, defocus curves, stereopsis, and patient satisfaction were assessed. Results: At 3 months, mean logMAR UDVA was 0.07 ± 0.09 in EDOF IOL eyes, 0.12 ± 0.11 in DMF IOL eyes, and 0.02 ± 0.05 in both eyes. UIVA was 0.11 ± 0.11 in EDOF IOL eyes, 0.16 ± 0.12 in DMF IOL eyes, and 0.04 ± 0.07 in both eyes. UNVA was 0.25 ± 0.15 in EDOF IOL eyes, 0.22 ± 0.16 in DMF IOL eyes, and 0.13 ± 0.13 in both eyes. Thirty patients(81.1%) were more than satisfied with near vision, and 8 patients(21.6%) complained of severe glare and halo. Spectacle independence for near vision was achieved in 34 patients(91.9%), and 31 patients(83.8%) had better than a 50 second arc of stereopsis. Conclusion: Mix-and-match cataract surgery with EDOF and DMF IOL implantation provided good visual outcomes through all distances. Also excellent patient satisfaction was achieved with high level of spectacle independence and minimal photic phenomena.

The involvement of macular function in its preganglionic elements, during the neurodegenerative process of multiple sclerosis (MS), is controversial. In this case-control observational and retrospective study, we assessed multifocal electroretinogram (mfERG) responses from 41 healthy Controls, 41 relapsing-remitting MS patients without optic neuritis (ON) (MS-noON Group), 47 MS patients with ON: 27 with full recovery of high-contrast best corrected visual acuity (BCVA) (MS-ON-G Group) and 20 with poor recovery of BCVA (MS-ON-P Group). MfERG N1 and P1 implicit times (ITs), and N1-P1 response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0-5° (R1), 5-10° (R2), 10-15° (R3), 15-20° (R4), 20- 25° (R5), and from retinal sectors [superior, nasal, inferior and temporal] between 0-15° and 0- 25°. In MS-ON-P Group, mean mfERG RADs detected from R1 (0-5°) and from the central nasal quadrant (0-15°) were significantly reduced (p<0.01) with respect to those of Control, MS-noON and MS-ON-G Groups. No other significant differences between Groups for any mfERG parameters were found. Our results suggest that in MS, exclusively after ON with poor recovery of BCVA, the neurodegenerative process can induce dysfunctional mechanisms involving photoreceptors and bipolar cells of the fovea and of the more central nasal macular area.

Background. Artificial Intelligence (AI) is an advanced technology for the latest 20 years. Machine learning (ML) and deep learning (DL) are the major innovations for AI, which has been applied for multiple fields. Ophthalmology has become to be one of the most significant disciplines for human healthcare. Methodology. This study utilizes methods of text mining and bibliometric analysis to explore applications of AI to ophthalmology. 179 related articles from Web of Science (WOS) and 96 papers from China National Knowledge Infrastructure (CNKI) are explored during the period of 2000 to 2021. A descriptive analysis of major trends, journal releasing, topic mapping and quotation relationships is implemented in this paper. Leading authors, journals, institutions, nations and references in the related research are identified. Results. Findings show that the application of AI technologies in ophthalmologic diagnosis with optical coherence tomography (OCT) fundus images is the core topic for this area’s studies, especially for diabetic retinopathy (DR), aged macular degeneration (AMD) and glaucoma. It is also be predicted as the core direction over the recent years. Besides, The USA, England and China is the most competitive countries in this scientific filed. Journals of Ophthalmology, Investigative Ophthalmology and Visual Science, Eye, Acta Ophthalmologica and Scientific Reports are the top five journal related to the research area. There is a significant difference between WOS and CNKI databases pertaining to the application of Artificial Intelligence (AI) to ophthalmology, especially for the historic development, topic mapping and discipline category. Finally, the potential academic value of interdisciplinary subject of “AI in Ophthalmology” and tradition Chinese medicine (TRM) is discussed. Limitations and suggestions for the future research is indicated at the end of this paper.

Purpose: To derive and provide analytic formulas for accommodative gain of presbyopia eyes. via sclera ablation and/or thermal shrinkage such that lens is reshaped an/or its positon is shifted. New mechanisms are also proposed. Study Design: To increased accommodation of presbyopia. Place and Duration of Study: New Taipei City, Taiwan, between June, 2021 and July, 2021. Methodology: Accommodation gain is calculated by a 4-component theory, in which the rate functions are derived by an effective eye model for the change of anterior curvature of the lens and its anterior shift. The measured data of accommodative response of the lens versus the lens curvature change and anterior shift are analyzed. The measured net change of the posterior vitreal zonules (PVZ) length and the space between the ciliary body and lens (CLS) during the accommodation are also analyzed. Results: The accommodative gain (AG) is mainly due the change of lens anterior curvature and its anterior shift. The AG per diopter change of the reshaped lens is 0.62 to 0.68 by our formulas, comparing to the measured average value M'=0.69. The efficacy of LASA (or AG) is proportional to the amount of scleral tissue removed (or shrinkaged), such that more space is produced for the change of PVZ and CLS from a UCS to AS for accommodation. Conclusion: The AG is proportional to the amount of scleral tissue removed (or shrinkaged), such that more space is produced for the change of PVZ and CLS from a UCS to AS for accommodation.

Anterior segment dysgenesis (ASD) encompasses a wide spectrum of developmental abnormalities of the anterior ocular segment, including congenital cataract, iris hypoplasia, aniridia, iridocorneal synechiae, as well as Peters, Axenfeld, and Rieger anomalies. Here, we report a large five-generation Caucasian family exhibiting atypical syndromic ASD segregating with a novel truncating variant of FOXC1. The family history is consistent with highly variable autosomal dominant symptoms including isolated glaucoma, iris hypoplasia, aniridia, cataract, hypothyroidism, congenital heart anomalies, and cystic kidney disease. Whole exome sequencing revealed a novel variant [c.313_314insA; p.(Tyr105*)] in FOXC1 that disrupts the alpha-helical region of the DNA-binding forkhead box domain. In vitro studies using a heterologous cell system revealed aberrant cytoplasmic localization of FOXC1 harboring the Tyr105* variant, likely precluding downstream transcription function. Meta-analysis of the literature highlighted the intrafamilial variability related to FOXC1 truncating alleles. This study highlights the clinical variability in ASD and signifies the importance of combining both clinical and molecular analysis approaches to establish a complete diagnosis.

Ocular drug delivery is one of the most challenging administration routes due to the very low drug bioavailability. In this work, we produce and characterize mucoadhesive mixed polymeric micelles (PMs) made of chitosan and poly(vinyl alcohol) backbones graft-hydrophobized with short poly(methyl methacrylate) blocks and use them to encapsulate cannabidiol (CBD), an anti-inflammatory cannabinoid. CBD-loaded mixed PMs are physically stabilized by ionotropic crosslinking of the CS domains with sodium tripolyphoshate and spray-drying. These mixed PMs display CBD loading capacity of 20% w/w and sizes of 100-200 nm, and spherical morphology (cryogenic-transmission electron microscopy). The good compatibility of the unloaded and CBD-loaded PMs is assessed in a human corneal epithelial cell line. Then, we confirm the permeability of CBD-free PMs and nanoencapsulated CBD in cornea cell monolayers under liquid-liquid and air-liquid conditions. Overall, our results highlight the potential of these polymeric nanocarriers for ocular drug delivery.

Purpose: To create a highly balanced comparison of ab interno trabeculectomy (Trabectome, AIT) and trabecular bypass stenting (iStent, TBS).Setting: Eye and Ear Institute, Pittsburgh, Ross Eye Institute, Buffalo, and Glaucoma Associates of Texas, Dallas, USA.Design: Retrospective Exact Matching analysis.Methods: AIT and TBS patients were included from three large glaucoma practices. The primary outcome measure was the unmedicated IOP ≤ 21 mmHg at 2-year follow-up visit. A secondary measure was unmedicated IOP reduction ≥ 20% at 2 years. Patients were matched by baseline IOP, the number of glaucoma medications and glaucoma type using Exact Matching and by age using Nearest Neighbor matching. Patients without a close match were excluded. All surgeries were combined with phacoemulsification. Results: 154 AIT and 110 TBS eyes were analyzed. 48 AIT patients were exactly matched to 48 TBS patients. Both groups had a baseline IOP of 15.3±3.1 mmHg. At 24 months, the mean IOP was 13.9±3.3 for AIT versus 16.8±2.8 mmHg for TBS (p=0.04), while the number of medications was 0.7±1.0 for AIT versus 1.7±1.2 for TBS (p=0.04). The proportion of subjects achieving IOP ≤ 21 mmHg without medications at 24 months was 53% in AIT versus 16.6% in TBS (P < 0.05). At 24-month follow up 17.6% of patients in AIT had ≥ 20% IOP reduction without medication versus no patient in TBS. Conclusions: An Exact Matching comparison of AIT and TBS demonstrated greater IOP reduction with fewer medications in AIT.

Glaucoma is a blinding disease largely caused by increased resistance to drainage of fluid from the eye’s anterior chamber, resulting in elevated intraocular pressure (IOP). A major site of fluid outflow regulation and pathology is the trabecular meshwork (TM) at the entrance of the eye’s drainage system. We aimed to characterize the structural and functional properties of a newly developed tissue-engineered anterior segment eye culture model. We hypothesized that repopulation of a decellularized TM with non-native TM cells could restore aspects of normal TM. The decellularization protocol removed all cells and debris while preserving the ECM. Seeded cells localized to the TM region and progressively infiltrated the meshwork ECM. Cells reached a distribution comparable to control TM after four days of perfusion culture. After a perfusion rate increase challenge, tissue-engineered cultures reestablished normal IOPs (reseeded = 13.7±0.4 mmHg, decellularized = 35.2±2.2 mmHg, p < 0.0001). eGFP expressing CrFK control cells caused a high and unstable IOP (27.0±6.2 mmHg). In conclusion, we describe a readily available, storable, and biocompatible scaffold for anterior segment perfusion culture of non-native cells. Tissue-engineered organs demonstrated similarities to native tissues and may reduce the need for scarce donor globes in outflow research.

Infectious keratitis (IK) represents a major cause of corneal blindness. This study aims to investigate the demographics, risk factors, microbiological characteristics and antibiotic susceptibility patterns of IK in Taiwan over the past 15 years. A retrospective population-based study was conducted using the Chang Gung Research Database. Patients with IK were identified by diagnostic codes for corneal ulcer from 2004 to 2019. Of 7807 included subjects, 45.2% of patients had positive corneal cultures. The proportion of contact lens-related IK declined, while that of IK related to systemic diseases grew. The percentage of isolated gram-positive bacteria surpassed that of gram-negative bacteria in the 15-year period. The prevalence of Pseudomonas aeruginosa showed a decreasing trend (p = 0.004), whereas coagulase-negative Staphylococcus (CNS) and Propionibacterium species were increasingly detected (p &lt; 0.001). Overall, the trend of antibiotic susceptibility of both gram-positive and gram-negative bacteria did not change throughout the study period. The susceptibility to the test antibiotics maintained over 90% in gram-negative isolates during 15 years. Vancomycin preserved 100% susceptibility to all gram-positive isolates. Since most tested antibiotics exhibited stable susceptibility over decades, this study reinforced that fluoroquinolones and fortified vancomycin continue to be good empiric therapies for treating bacterial keratitis in Taiwan.

We compared the functional and morphologic effects in the loading dose between patients with treatment-naïve neovascular age-related macular degeneration treated with either intravitreal aflibercept (IVA) or intravitreal faricimab (IVF) injection in clinical settings. This retrospective study included 30 eyes from 28 patients who started IVA treatment between June and September 2022 and 30 eyes from 29 patients who started IVF treatment between October 2022 and March 2023. The mean best corrected visual acuity (BCVA) significantly improved from pre-treatment after loading dose in the IVA group (from 0.46 ± 0.46 to 0.36 ± 0.37, p=0.0047) and not in the IVF group (from 0.46 ± 0.41 to 0.44 ± 0.45, p=0.60). The mean central retinal thickness (CRT) significantly improved in both groups. The proportion of eyes with residual exudative change was greater in the IVF group than in the IVA group at 2 months after the first treatment. (p=0.026) We further analyzed the patients who obtained complete resolution of exudative changes after the loading dose. The IVA group had a significant improvement in BCVA, whereas the IVF group did not p=0.0047 and 0.20, respectively) Although IVA and IVF significantly improved the CRT, the BCVA improved significantly in IVA group and not in IVF group.

Background and Objectives: Mucilaginous substances from plant extracts are known to be able to support the lubricating effect of hyaluronic acid (HA) in dry eye disease (DED). In this pilot study, the combined lubricating effect of HA and mallow extract (Malva sylvestris L.) in patients with DED was assessed. Materials and Methods: 20 patients at 5 ophthalmological practices in Italy were treated with eye drops, containing HA and mallow extract on the one hand, and with eye drops containing HA only, on the other hand, in a two-period crossover design. As primary endpoints, the tear film breakup time (TBUT), the reduction of lissamine green staining of the ocular surface (Oxford Scheme, OS), and the safety and efficacy assessment by the ophthalmologists were evaluated. As secondary variables, the patient symptom score, the ocular surface index (OSDI), and the satisfaction, preference and efficacy judgement by the patients were evaluated. All data were analysed descriptively in addition to an exploratory analysis of the target variables. Results: Both products were well tolerated. There were no statistically significant differences, with regard to the TBUT, OS and OSDI, between both treatments. Anyway, the efficacy and safety assessments by the ophthalmologists and the patients showed results in favour of the combined product. Conclusion: The addition of mallow extract to HA containing eye drops enhances the treatment of DED at least with respect to subjective measurements. Further assessments will have to be done to prove and explain this observation in terms of measurable parameters, e.g. markers for inflammatory cytokines.

Fungal keratitis (FK) is a serious ocular infection that often poses significant diagnostic and therapeutic dilemmas. This study aimed to examine the causes, clinical characteristics, outcomes, and prognostic factors of FK in the UK. All culture-positive and culture-negative presumed FK (with complete data) that presented to Queen’s Medical Centre, Nottingham, and Queen Victoria Hospital, East Grinstead, between 2011 and 2020 were included. A total of 117 patients (n=117 eyes) with FK were included in this study. The mean age was 59.0±19.6 years (range, 4-92 years) and 51.3% patients were female. Fifty-three fungal isolates were identified from 52 (44.4%) culture-positive cases, with Candida spp. (33, 62.3%), Fusarium spp. (9, 17.0%), and Aspergillus spp. (5, 9.4%) being the most common organisms. Ocular surface disease (60, 51.3%), prior corneal surgery (44, 37.6%), and systemic immunosuppression (42, 35.9%) were the three most common risk factors. Hospitalisation for intensive treatment was required for 95 (81.2%) patients, with a duration of 18.9±16.3 days. Sixty-six (56.4%) patients required additional surgical interventions for eradicating the infection. Emergency therapeutic/tectonic keratoplasty was performed in 29 (24.8%) cases, though 13 (44.8%) of them failed at final follow-up. The final corrected-distance-visual-acuity (CDVA) was 1.67±1.08 logMAR. Multivariable logistic regression analyses demonstrated increased age, large infiltrate size (>3mm), and poor presenting CDVA (<1.0 logMAR) as significant negative predictive factors for poor visual outcome (CDVA of <1.0 logMAR) and poor corneal healing (>60 days of healing time or occurrence of corneal perforation requiring emergency keratoplasty; all p<0.05). In conclusion, FK represents a difficult-to-treat ocular infection that often results in poor visual outcome, with a high need for surgical interventions. Innovative treatment strategies are urgently required to tackle this unmet need.

Glaucoma is a leading cause of blindness. Surgical and pharmacological treatment of glaucoma aims to lower the intraocular pressure (IOP) and preserve visual function. The severe acute res-piratory syndrome coronavirus 2 pandemic has placed a strain on the healthcare system. We aimed to compare the quantity, type of anti-glaucoma surgeries, and the disease stage before and during the coronavirus disease pandemic. We analyzed 362 eyes of 306 patients and 172 eyes of 149 patients from the pre-pandemic and pandemic groups, respectively. The number of an-ti-glaucoma surgeries was halved during the pandemic compared to a similar pre-pandemic pe-riod, with a significant difference in the procedural structures between the two groups (p<0.001). The most common procedures in the pre-pandemic group were Ex-Press implantation (33.7%) and trabeculectomy (31.5%). Within the pandemic group, half of the eyes underwent tra-beculectomy (50.0%), followed by Preserflo microshunt (11.6%). A significant difference in the average IOPs was revealed among patients who qualified for surgery 22.21 ± 7.83 mmHg in the pre-pandemic group and 25.16 ± 9.48 mmHg in the pandemic group; p<0.001). There was no significant difference in the best corrected visual acuity between the groups (p=0.263). Glaucoma treatment remained relatively accessible during the pandemic.

A 31-year-old male noticed blurred vision in his right eye for five days with no obvious predisposing causes, accompanied by mild dizziness. No obvious nodular lesions were found in the body. The patient’s binocular visual acuity was 20/20. Fundus photography showed the optic nerve swelling and radial superficial retinal hemorrhage of both eyes. Blood panel, urine routine, liver, and kidney function were all normal. Total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein were all in the normal limits. Head MRI showed a mass in the right temporal lobe, clear boundary, and multiple separations, which thinned and disappeared closer to the skull. The right temporal lobe and lateral ventricle were all compressed, with the midline structure shifted to the left. The patient was then transferred to Neurosurgery. During the operation, we observed the tumor had invaded the skull. The actual size of the tumor was 5.6 cm × 7.5 cm × 10.1 cm. Histology revealed foam cell accumulation in the mucous connective tissue of the right temporal lobe. The immunohistochemistry showed: CD34 (+), CD99 (+), EMA (−), GFAP (−), IDH-1 (−), Ki-67 (+) index about 10%, Oliga-2 (−), PR (−), S-100 (−), Vim (+), β-Catenin (+), CD1a (−), CD68 (+). Three months after the removal of the tumor, the visual acuity of both eyes was 20/20; The visual fields were normal, the optic disc edema and retinal hemorrhages had disappeared. MRI indicated the midline structure was back to normal.

Dry eye disease (DED) most commonly caused by evaporative subtypes and mainly induced by meibomian gland dysfunction (MGD). Intense pulsed light (IPL) combined with meibomian gland expression (MGX) is noninvasive treatment for improvement of ocular discomfort symptoms and MGD. In this prospective study between November 2020 and May 2022, the patients met the criteria of both ocular surface disease index (OSDI) ≥13 scores and standardized patient evaluation of eye dryness (SPEED)≥ 8 scores were enrolled in Kaohsiung Veteran General Hospital. Three separate treatment sessions of IPL therapy combined with MGX administered to the lower lids with an interval of 28 days. Further tear film assessment included lipid layer thickness (LLT), tear meniscus height (TMH), non-invasive tear break-up time (NIBUT), meibomian gland loss (MGL) either beforeor after 1st and 3rd IPL therapy combined with MGX. Besides, lissamine green staining and pain scores were also recorded. We totally enrolled 37 patients of 74 eyes. Men accounted for 18.92% (7/37). The mean age was 54.51 ± 11.72 years. The mean OSDI scores were 58.12 ± 22, while the SPEED scores were 17.03 ± 5.98. The mean Schirmer’s test was 3.66 ± 2.43 mm. After three sessions IPL treatment with MGX, the OSDI, SPEED, LLT, TMH, MGL, MGXS and pain scores were significantly improved. For the MGX scores (MGXS) ≤20 group, MGL and lissamine green scores showed significant improvements. For the MGXS >20 group, TMH and dry spot rate revealed statistically improvement. Noninvasive IPL therapy with MGX statistically improved not only dry eye symptoms but also tear film assessments.

Purpose: To evaluate seasonal variation in intra-ocular pressure (IOP) with and without short tear break-up time (SBUT, BUT ≤ 5 s). Methods: This study enrolled 176 patients who visited one of six eye clinics in Japan for IOP measurement at every season. The mean patient age was 67.9 years, including 79 males. We compared the seasonal variation in IOP (mean ± SD) across spring (Mar-May), summer (Jun-Aug), fall (Sep-Nov), and winter (Dec-Feb). Results: The IOP (mmHg) in winter and summer, respectively, was 12.8 ± 3.7 and 12.8 ± 3.1 for non-glaucoma patients without SBUT (n = 47, P = 0.964), 14.8 ± 3.4 and 13.3 ± 3.4 for non-glaucoma patients with SBUT (n = 57, P < 0.001), 14.3 ± 3.2 and 14.1 ± 3.4 for glaucoma patients without SBUT (n = 36, P = 0.489), and 13.3 ± 3.0 and 11.6 ± 2.9 for glaucoma with SBUT (n = 36, P < 0.001). Seasonal variation was largest across the seasons in the glaucoma with SBUT group, and the magnitude of seasonal variation correlated with BUT (β = 0.228, P = 0.003). Conclusions: Seasonal variation tended to be larger in patients with SBUT than those without SBUT.

Purpose: The evaluation of the efficacy of topical hypotensive treatment and/or systemic corticosteroids therapy in patients with elevated intraocular pressure and Graves’ orbitopathy (GO). Methods: 172 eyes in 86 individuals with duration of GO ≥ 3 months, intraocular pressure in either eye ≥ 25.0 mmHg and GO ranked ≥ 3 at least in one eye in modified CAS form, were included. The study subjects were divided into three treatment subgroups: subgroup I was administered latanoprost QD; subgroup II was administered a combined preparation of brimonidine and timolol BID; subgroup III was the control group, not receiving any topical hypotensive treatment. All the study participants received systemic treatment – intravenous corticosteroid therapy at the same dose, according to the EUGOGO guideline Results: On the final visit, the mean IOP value was significantly lower in all treatment subgroups comparing to the initial values. In both subgroups receiving topical treatment the IOP reduction was higher than in the control group receiving systemic corticosteroids only. However, the latanoprost eye drops decreased intraocular pressure more effectively than drops containing brimonidine and timolol. Conclusion: Topical ocular hypotensive treatment is effective in reducing intraocular pressure in GO and decreases intraocular pressure more effectively than systemic corticosteroid therapy alone.

Purpose: We evaluated the outcomes of fluid-gas exchange (FGE) for long-term flap closure of idiopathic macular hole (MH) after the inverted internal limiting (ILM) flap technique. Methods: We included eyes showed flap closure without complete MH closure, connection of the apart macular tissue, 1 month postoperatively after the inverted ILM flap technique. The eyes stayed at flap closure at 2 months postoperatively further underwent in-office FGE with 16% C3F8. Results: Among 10 eyes, 5 eyes (50%) showed flap closure at 2 months postoperatively further underwent FGE for complete MH closure while the remaining 5 eyes (50%) progressed directly at 2 months postoperatively. The improvement in vision of all flap closure from baseline was significant (p=0.015), with the mean baseline vision was 1.19 [Snellen equivalent (SE), 20/307] ± 0.52 logMAR and the mean final vision being 0.63 (SE, 20/85) ± 0.38 logMAR. The group that underwent FGE showed a better final vision of 0.45 (SE, 20/75) ± 0.23 logMAR than the group that didn’t undergo FGE (0.81 [SE, 20/128] ±0.44 logMAR). All eyes achieved complete MH closure, including the eyes that underwent FGE in a mean period of 5.60 months (range 3-10 months) after the inverted ILM flap technique. The eyes that underwent FGE achieved higher rate of foveal restoration [complete external limiting membrane (ELM): 80%; complete ellipsoid zone (EZ): 60%] than those that didn’t receive FGE (complete ELM: 40%; complete EZ: 10%). Conclusions: Eyes that underwent FGE accelerated complete MH closure and showed better final vision and fovea l restoration.

Childhood glaucoma encompasses congenital and juvenile primary glaucoma, which are heterogeneous, uncommon, and irreversible optic neuropathies leading to visual impairment with poorly understood genetic basis. Our goal was to identify gene variants associated with these glaucoma types by assessing the mutational burden in 76 matrix metalloproteinase-related genes. We studied 101 childhood glaucoma patients with no identified monogenic alterations using next-generation sequencing. Gene expression was assessed through immunohistochemistry. Functional analysis of selected gene variants was conducted in cultured cells and in zebrafish. Patients presented a higher proportion of rare variants in four metalloproteinase-related genes, including CPAMD8 and ADAMTSL4, compared to controls. ADAMTSL4 protein expression was observed in the anterior segment of both the adult human and zebrafish larvae's eye, including tissues associated with glaucoma. In HEK-293T cells, expression of four ADAMTSL4 variants identified in this study showed that two variants (p.Arg774Trp and p.Arg98Trp) accumulated intracellularly, inducing endoplasmic reticulum stress. Additionally, overexpressing these ADAMTSL4 variants in zebrafish embryos confirmed partial loss-of-function effects for p.Ser719Leu and p.Arg1083His. Double heterozygous functional suppression of adamtsl4 and cpamd8 zebrafish orthologs resulted in reduced volume of both the anterior eye chamber and lens within the chamber, supporting a genetic interaction between these genes. Our findings suggest that accumulation of partial functional defects in matrix metalloproteinases-related genes may contribute to increased susceptibility to early-onset glaucoma and provide further evidence supporting the notion of a complex genetic inheritance pattern underlying the disease.

Purpose: We hypothesized that a recently introduced epibulbar micro-shunt (PRESERFLO, P) produces nycthemeral (24h) intraocular pressure (IOP) profiles different from ab-interno trabeculectomy (Trabectome, T). P is a flow restrictor that drains fluid into the sub-tenon space. In contrast, T increases conventional outflow, which is limited by episcleral venous pressure. Methods: In this prospective cohort, we analyzed 68 patients (34 P and 34 T) who presented for 24-h IOP monitoring 6 to 12 months after surgery. IOP and tonographic outflow facility were measured in the habitual position using a pneumatonometer. The IOP variation was considered the primary outcome measure. Glaucoma medications were also compared. Results: P had a higher baseline IOP than T (24.8±10.0 vs. 17.3±7.9 mmHg, p=0.001). Postoperatively, P and T had similar nycthemeral IOP profiles, but IOP in P was significantly lower than in T, except at 4 pm. P had a lower absolute IOP variation than T (5.8±2.6 vs. 7.1±2.7 mmHg, p=0.049). The relative IOP variation was similar in both (34.8±13.2 vs. 37.2±13.1, p=0.45) as was the tonographic outflow facility (0.35±0.23 vs. 0.26±0.18 µl/min/mmHg, p=0.097). Conclusion: Nycthemeral IOP profiles of P and T were similar, but P had lower IOPs and less variation than T. This could reflect how T, unlike P, is more impacted by habitual, positional factors, especially at night.

Increased screen time during the COVID-19 pandemic and the accelerated incorporation of technology into daily practices have directly contributed to the increased prevalence of eye disease. The human eye is not built for continual technological use and must adjust to exposure to digital screens. Overexposure to technology can result in eye strain and an increased risk of eye diseases such as myopia with complications later in life, including retinal tears, cataracts, and macular degeneration. As vision and ocular diseases become more prevalent, the study of eye diseases, including their causes and treatments, is especially relevant. There is a need to prevent ocular diseases before they become a burden to individuals, their families, and their communities by better understanding the pathophysiology of ocular diseases. Several ocular diseases are thought to be caused by imbalances in reactive oxygen species (ROS) and autophagy. ROS refers to a class of highly reactive oxygen-containing molecules that can undergo damaging reactions with other molecules in the cell. Autophagy is a cellular process of self-eating whereby damaged, harmful, or dead material in cells is broken down to maintain cellular homeostasis. This paper discusses the role of ROS and autophagy in the pathogenesis of computer vision syndrome (CVS), digital eye strain (DES), myopia, cataracts, glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve crush injury (OCN), optic nerve gliomas, and retinoblastoma. Lifestyle changes such as limiting screen time, ensuring adequate exposure to evening sunlight, and using blue light protection measures or protective eyewear are important in the prevention of eye disease. Nutrition also contributes significantly to eye health. A balanced diet rich in vitamins and antioxidants may help to prevent ROS and autophagy imbalance-induced eye disease. Medical and surgical treatments become necessary when preventative measures fail. This paper also addresses how government measures to decrease the onset of eye disease, including targeted programs to increase access to fresh vegetables and fruits in food deserts, are a critical macro-level avenue to reduce eye disease prevalence in the US, which according to the National Eye Institute, costs $139 billion yearly.

Aim: To investigate the application of anterior and posterior corneal higher order aberrations (HOAs) in detecting keratoconus (KC) and suspect keratoconus (SKC). Method: This is a retrospective, case-control study which evaluated non-ectatic (normal) eyes, SKC eyes, and KC eyes. The Sirius Scheimpfug (CSO, Italy) analyzer was used to measure HOAs of the anterior and posterior corneal surfaces. Sensitivity, specificity and area under receiver operating characteristic curve (AUC) were calculated. Results: Two-hundred and twenty eyes were included in the analysis (normal n = 108, SKC n= 42, KC n= 70). Receiver operating characteristic (ROC) curve analysis revealed a high predictive ability for anterior corneal HOAs parameters: Root mean square (RMS) total corneal HOAs, RMS trefoil and RMS coma to detect keratoconus (AUC > 0.9 for all). RMS Coma (3, ±1) derived from the anterior corneal surface was the parameter with the highest ability to discriminate between suspect keratoconus and normal eyes (AUC = 0.922; cutoff > 0.2). All posterior corneal HOAs parameters were insufficient in discriminating between SKC and normal eyes (AUC < 0.8 for all). In contrast, their ability to detect KC was excellent with AUC of > 0.9 for all except RMS spherical aberrations (AUC = 0.846). Conclusion: Anterior and posterior corneal higher order aberrations can differentiate between keratoconus and normal eyes, with a high level of certainty. In suspect keratoconus disease however, only anterior corneal HOAs, and in particular coma-like aberrations, are of value. Corneal aberrometry may be of value in screening for keratoconus in populations with a high prevalence of the disease.

Purpose is to o review the pathogenic mechanism for ocular hypertension and glaucoma development after pars plana vitrectomy. Both acute and chronic causes are considered and special attention is paid to the theories and clinical evidence on the risk of developing Open Angle Glaucoma (OAG) after Pars Plana Vitrectomy (PPV). Most existing scientific literature on the issue agree on the role of ascorbate as an oxygen scavenger within the vitreous chamber. Oxygen tension in the vitreous and anterior chamber is maximum inn proximity of the retinal surface and endothelium, respectively and steeply decreases toward the lens; on both sides, and trabeculate. Vitreous removal and, to a lesser extent, liquefaction, greatly reduces oxygen tension gradient in vitreous chamber while cataract extraction has similar effects on anterior chamber oxygen gradients. Oxygen derivatives originated from the cornea and retina are actively reduced by the vitreous gel and/or the crystalline lens. Vitreous removal and cataract extraction reduce drastically this function. Most reported clinical series confirm this hypothesis although protocol difference and follow-up length greatly impact the reliability of results.

Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.

(1)Aims of the study: calculating the underreporting ratio for two different medications, a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (antiglaucoma) and a fixed combination of sodium hyaluronate 0.1% + chondroitin sulfate 0.18% (artificial tear) and characterizing the features influencing the reporting of adverse drug reactions (ADRs) in spontaneous reporting; (2) Methods: the underreporting ratio was calculated by comparing the adverse drug reactions reported in the spontaneous reporting database for every 10,000 defined daily doses marketed and the adverse drug reactions from an active surveillance study for every 10,000 defined daily doses used for different drugs (antiglaucoma and artificial tear). The factors related to the report in spontaneous reporting through statistical tests were also determined; (3) Results: The underreporting ratio of spontaneous reporting was 0.006029% for antiglaucoma and 0.003552% for artificial tear; additionally, statistically significant differences were found for severity, unexpected adverse drug reactions, and incidence of adverse drug reactions in females; (4) Conclusions: The underreporting ratio of ADRs related to ophthalmic medications indicates worry since the cornerstone of pharmacovigilance focuses on spontaneous reporting. Besides, since underreporting seems to be selective, the role of certain aspects like gender, seriousness, severity, and unexpected ADRs, must be considered in future research.

To investigate factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The main outcome was an extension of the treatment interval after 6 months, and factors related to the success or failure of the extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes of 43 patients. Extended dosing intervals of more than 2 weeks were identified in 14 eyes (32.6%). A short dosing interval before the switch, the absence of polypoidal lesions, and a thin central choroidal thickness before the switch were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend from existing dosing intervals.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

Dry eye disease (DED) is a multifactorial disorder in which tear fluid homeostasis is lost, resulting in increased tear film osmolarity and ocular surface irritation. In Asia, the short tear film breakup time type-DED is common, and stabilization of the tear film is the first goal of treatment. Treatment of DED begins with eye drops. Until now, artificial tears and steroid eye drops have been the main treatment for DED. However, artificial tears require frequent administration of eye drops and thus pose adherence problems, while steroids have problems with side effects (cataracts, increased intraocular pressure). This review evaluates the new generation of DED therapies in Asia based on what is known about them and demonstrates that they are more effective for DED than traditional therapies such as artificial tears and steroids. Based on these considerations, it is proposed that the optimal treatment for DED in Asia is the initial application of mucin secretion enhancing eye drops (long-acting diquafosol) and oral supplements, and if additional treatment is needed, cyclosporine eye drops and the adjunctive therapies presented in this review are added.

Starvation of photoreceptors induced by reduced dysregulated ocular blood flow (OBF) is proposed as a common pathway for pathogenesis of retinitis pigmentosa (RP). The current study evaluated the safety and efficacy of ophthalmic nerve stimulation (ONS) as an OBF neuromodulator, combined with ascorbic acid (AA) as a potent anti-oxidant in treatment of RP. Additionally, the initial characteristics of rod responders were identified. Forty participants with simple RP, were enrolled in a prospective open-label intervention. The severity of the disease was clinically graded into five stages. Patients with established diagnosis of RP; aged ≥ 4 years, with BCVA ≥ 20/400 were included. All participants were daily treated with bilateral ONS sessions combined with systemic AA for two weeks. The primary efficiency endpoint was 6 months’ changes in scotopic vision as measured by a 10-items, 100 points, Low Luminance Questionnaire- (LLQ-10). The secondary efficiency points included best corrected visual acuity (BCVA) and contrast sensitivity (CS). Rod responders were defined by ≥ 25points increment of LLQ-10 score. The results showed that ONS combined with AA treatment significantly improved night vision, BCVA and CS in patients with RP. At 6-month visit, twenty-four (60%) patients were identified as rod responders and 16 (40%) patients were non-responders. The mean change in LLQ-10 score was (46.35 ±16.81) in rod responders versus (4.9 ± 7.6) in non-responders (P < 0.0001). A clinically significant improvement of BCVA (≥0.2 logMAR) and CS (≥0.3 log unit) were demonstrated in 44.4% and 56.1% of eyes of rod responders respectively. Collectively, this study sheds light on determinants of rod responsiveness which include patients’ age, duration of night blindness and the stage of RP. It also highlights two therapeutic scenarios; an early disease -modifying intervention that restore night vision and reverse the disease process and a late cone rescue intervention that improve/maintain central vision.

In this paper we use quantum machine learning to detect and classify ocular diseases across age related macular degradation, cataract, diabetic, glaucoma, hypertension, and patological myopia categories versus a control group. We analyze fundus imagery from 1000 patients. Early findings indicate there may be benefit in terms of accuracy and loss function minimization of 2.07% and 1.979x respectively compared to a similar method implemented using traditional computers.

Progressive loss of retinal ganglionic cells (RGC) causes blindness in glaucoma. Elevated intraocular pressure (IOP) is the most important, treatable risk factor. Currently, the management of glaucoma is centred at reducing the IOP, and drugs in the form of topical drops are the first line of management. Drugs reduce IOP either by suppressing aqueous humour secretion or improving the aqueous humour outflow. Newer drugs added during the past three decades to the armamentarium of glaucoma treatment have targeted the aqueous outflow. With an evolving understanding of the pathogenesis of glaucoma, the role of 24-hour IOP control and other IOP-independent risk factors affecting ocular blood flow and RGC toxicity is also recognised. The role of available drugs in controlling IOP over 24-hours is being evaluated. Improvement of ocular blood flow and neuroprotection are seen as potential drug targets in preventing the loss of RGC. In this article, we review the pharmacotherapy of glaucoma based on current therapeutic principles.

OCTA is an imaging modality used in the assessment of the retinal vasculature. It operates on the principle of coherence tomography used in standard OCT with the addition of delineating the retinal vascular. This provides a modern non-invasive retinal vascular imaging method compared to conventional dye-based imaging. High quality depth resolution of the superficial and deep capillary networks is possible on OCTA whereas this was not possible prior. OCTA may be limited by image quality degradation from factors such as motion artefact or media opacities, and therefore may not be the investigation of choice for all patient groups. There are multiple potential clinical applications for OCTA in retinal and choroidal vascular disease. Ongoing research is necessary to substantiate the more widespread use of OCTA due to its significant cost burden compared to current modalities.

Retinitis pigmentosa-59 (RP59) is a rare, recessive form of RP, caused by mutations in the gene encoding DHDDS (dehydrodolichyl diphosphate synthase). DHDDS forms a heterotetrameric complex with Nogo-B Receptor (NgBR; gene NUS1) to form a cis-prenyltransferase (CPT) enzyme complex, which is required for synthesis of dolichol, which in turn is required for protein N-glycosylation as well as other glycosylation reactions in eukaryotic cells. Herein, we review the published phenotypic characteristics of RP59 models extant, with an emphasis on their ocular phenotypes, based primarily upon knock-in of known RP59-associated DHDDS mutations as well as cell type- and tissue-specific knockout of DHDDS alleles in mice. We also briefly review findings in RP59 patients with retinal disease and other patients with DHDDS mutations causing epilepsy and other neurologic disease. We discuss these findings in the context of addressing “knowledge gaps” in our current understanding of the underlying pathobiology mechanism of RP59, as well as their potential utility for developing therapeutic interventions to block the onset, or to dampen the severity or progression, of RP59.

Infectious keratitis (IK) is among the top 5 leading causes of blindness globally. Early diagnosis is key to guide an appropriate therapy to avoid complications such as vision impairment and blindness. Culture of corneal scrapes is the initial diagnostic test to grow and identify the causal organism. Alternative diagnostic tools include imaging such as with optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM). OCT’s advantage is its ability to accurately determine the depth and extent of the corneal ulceration, infiltrates and haze; therefore, characterizing the severity and progression of the infection. However, it is not a preferred choice in the diagnostic tool package for infectious keratitis. IVCM is a great aid in the diagnosis of fungal and Acanthamoeba keratitis with overall sensitivities of 66-74% and 80-100%, and specificity of 78-100% and 84-100%, respectively. Recently the use of deep learning (DL) models in IK has been shown to aid diagnosis via image recognition. Most of the studies that have developed DL models to diagnose the different types of IK have utilised photographs from digital camaras, slit-lamp images, or IVCM images. Some studies have used extremely efficient single DL algorithms to train their models and others used ensemble approaches. This technology is likely to assist in the diagnosis of IK in some years. Further work is needed to examine and validate the clinical performance of the DL models in the real-world setting and to evaluate whether this technology improves patient clinical outcomes. The scope of this review was to provide a recent update on the diagnostic imaging tools in IK

: Glaucoma is the most common cause of blindness, which significantly reduces quality of life. Most glaucoma cases are primary glaucoma; nevertheless, many patients suffer from glaucoma caused by drugs, such as corticosteroids. A comprehensive review of the risks associated with corticosteroid-induced glaucoma is limited. Therefore, we used the Japanese Adverse Drug Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency (PMDA) to analyze the risk factors associated with glaucoma and the trends and characteristics of corticosteroid-induced glaucoma. We did not find sex or age differences associated with the onset of glaucoma. Hierarchical clustering and principal component analysis revealed that triamcinolone acetonide and betamethasone sodium phosphate, which are used around the eyes in Japan, are more likely to induce intraocular pressure (IOP) elevation compared with other corticosteroids. Increased IOP is a direct cause of glaucoma. Based on these findings, it may be necessary to limit or avoid the use of these corticosteroids.

Background: Prismatic cover test (PCT) is a gold standard assessment of strabismus angle, however it has a significant number of disadvantages which are eliminated in Strabiscan device. Methods: Patients with strabismus (n = 30) and a group of healthy subjects (n = 30) were given a detailed history and underwent ophthalmologic examinations (best corrected visual acuity assessment, cycloplegic autorefractometry, biomicroscopic examination of anterior and posterior part of the eye). Each patient and healthy subjects were then subjected to the PCT, and then the presence of strabismus was detected, and its angle assessed using a Strabiscan demonstrator. Statistical analysis was done with Statistica software. Results: No statistically significant differences were noted in the measurements of strabismus angles made by the differing methods. Among the control group, using the Strabiscan demonstration device, low-angle latent strabismus ≤3PD was diagnosed in 83% of patients, and >3PD in 13% of patients. Those using the PCT, on the other hand, diagnosed latent strabismus ≤3PD in only 13% of patients, and latent strabismus with an angle >3PD in 13% of patients. Conclusion: The Strabiscan demonstration device provides quick and accurate assessment of the strabismus angle.

Biomechanics is a branch of biophysics that deals with mechanics applied to biology. The biomechanics of the cornea plays a significant role in managing patients with glaucoma. While evidence suggests a higher risk of glaucoma in patients with thin and stiffer corneas, it also affects the measurement of intraocular pressure (IOP). We reviewed the pertinent literature to help the understanding of corneal biomechanics and how it can help optimize clinical and surgical treatments and a better approach to diagnosing and managing patients with glaucoma.