Background and Objectives: Uveitis, a prevalent eye disorder characterized by inflammatory processes, often leads to cataract formation and significant visual impairment. This study aimed to evaluate preoperative conditions and postoperative outcomes following cataract surgery in uveitis patients. Materials and Methods: A retrospective study was conducted at the University Hospital Center Rebro Zagreb, Croatia, involving uveitis patients who underwent cataract surgery between 2013 and 2022. Eligible patients had uveitic cataracts affecting visual acuity or posterior segment visualization in a "quiet eye" and were disease-inactive for at least three months. Patients with certain preexisting ocular conditions were excluded. Data collected included patient demographics, uveitis type, preoperative therapy, preexisting lesions, and postoperative outcomes such as visual acuity, intraocular pressure, central macular thickness, and complications. Statistical analysis was performed to identify risk factors associated with complications. Results: The study included 105 patients. After cataract surgery, there was a significant improvement in visual acuity at various time points, with 90% of eyes showing improvement. Intraocular pressure decreased over time. Central macular thickness increased at three months post-surgery but remained stable thereafter. Early and late complications were observed in 52.4% and 63.8% of eyes, respectively. The most common complications were posterior capsular opacification, macular edema, and epiretinal membrane. Factors associated with complications varied between early and late stages but included age, age at onset of uveitis, and uveitis type. Conclusion: Cataract surgery in uveitis patients presents challenges but can lead to significant visual improvement. This study highlights the importance of careful patient selection, preoperative and postoperative inflammation management, and precise surgical techniques. Although complications were common, they were manageable, and most patients experienced improved vision, emphasizing the benefits of cataract surgery in this population. However, future investigations should address the study's limitations and further refine perioperative strategies.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syn-drome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by ab-normal retinal endothelial cell function – and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. The goals of this review are to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Purpose: To assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild to moderate dry eye disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Methods: Tolerability and safety were evaluated in 24 healthy subjects. Participants were in-structed to routinely apply one drop of the formulation three times a day in the study eye, for a period of two weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/ receiving the study formulation) or Control (Group 2/ Receiving HA 0.4% eye lubricant) groups, for 4 weeks. Assessments included MMP-9 positivity, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive tear film breakup time (NIF-BUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with a four-week follow-up was applied to the control group. Results: Healthy subjects receiving the study formulation exhibited good tolerability and no ad-verse events. Group 1 showed significant MMP-9 reduction (25% positivity rate) unlike Group 2 (87.5% positivity rate). Group 1 displayed improved CIC (33.3% vs. 0% SSD) compared to Group 2 (29.1%). OSDI and NIF-BUT scores improved in both groups (p < 0.001). Only Group 1 showed improved NIAvg-BUT and Schirmer’s test scores (p < 0.001), while Group 2 did not (p > 0.05). MMP-9-positive subjects shifted from 25% to 91.6% in Group 1 and 87.5% to 20.8% in Group 2 after the follow-up. Conclusion: The topical formulation containing helenalin from Arnica montana and hyaluronic acid is well tolerated and has a good safety profile. Our formulation reduces DED sympto-matology and modulates the ocular surface inflammatory process; this is evidenced by the en-hancement of CIC, the improvement of DED-related tear film status, and the reduction of MMP-9 positivity rate.

Growing incidence of myopia worldwide justifies the search for efficient methods of myopia prevention. Numerous pharmacological, optical, and lifestyle measures have already been utilized, but there remains a need to explore more practical and predictable methods for myopia control. This paper presents a review of the latest literature on preventing the progression of myopia using Defocus Incorporated Multiple Segments Spectacle Lenses (DIMSsl), Repeated Low-level Red-Light Therapy (RLRL), and the combination of low-dose atropine (0.01%) with orthokeratology lenses.

Background: The most frequent non-pigmented malignancy of the ocular surface is ocular surface squamous neoplasia (OSSN), which has a frequency of 0.03 to 1.9 per 100,000 people per year. It can be diagnosed histologically as anything from mild dysplasia to aggressive squamous cell carcinoma that affects both the conjunctiva and the cornea. The purpose of this study is to determine the distribution of ocular surface squamous neoplasia at a teaching hospital in South Western Uganda.Methods: In this retrospective study, we reviewed all records of patients with ocular surface squamous neoplasia from the Mbarara University of Science and Technology (MUST)/ Mbarara Regional Referral Hospital (MRRH) pathology laboratory in South Western Uganda, from January 2015- October 2021.Results: Of the 1,133 cases of ocular neoplasia seen during this time, OSSN composed of 26.7% (n=303). OSSN occurred mainly in females (59.1%). The most common OSSN was invasive squamous cell carcinoma (60.4%). The age range was 15-106 years while the mean was 39.99 years. The commonest affected age group was 30-44years (41.3%).Conclusion: The burden of OSSN is high. It primarily affects young adults and is frequently found in women. Squamous cell carcinoma makes up the majority of the disease.

Abstract: The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRa and GRb), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e. GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have lower expression of GRb, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. Increased expression of GRb can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. Endogenous expression of GRb in the TM may relate to differences in the development of GC-OHT among the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease modifying therapies to better treat these two sight threatening forms of glaucoma.

Background We aimed to compare the retinal, optic disc vascular density (ODVD) values, and acircularity index (AI) of patients with idiopathic macular telangiectasia type 2 (IMT) and healthy individuals using the optical coherence tomography angiography(OCTA) device. Methods The study included 39 patients with IMT and 37 healthy controls. The OCTA findings of the patients and controls were examined. Results The total, parafoveal and perifoveal vascular density of the superficial capillary plexus, choriocapillaris blood flow, inside-disc ODVD, retinal nerve fiber layer (RNFL), and retinal thicknesses were found to be statistically significantly lower and the foveal avascular zone value was statistically significantly higher in the IMT group compared to the control group (p=0.001, p=0.01, p=0.02, p=0.01, p=0.009, p=0.002, p=0.02, respectively).There was a statistically significant negative correlation between best-corrected visual acuity (BCVA) and AI (p=0.02), a statistically significant positive correlation between peripapillary vascular density and BCVA(p=0.04). Conclusion We consider that the lower retinal, choriocapillaris, and ODVD values, retinal and RNFL thicknesses in the patients with IMT compared to the controls were due to vascular damage, remodeling, fibrosis, proliferation, and Müller cell damage. Ellipsoid zone defect, AI, and peripapillary vascular density are important indicators in the evaluation of visual acuity in these patients.

Abstract Purpose: To analyze the correspondence between refractive astigmatism and corneal astigmatism in pseudophakic eyes with non-toric intraocular lenses. Setting: Yeouido St. Mary hospital, Seoul, South Korea Design: Evaluation of a diagnostic test instrument. Methods: This retrospective study included 95 eyes of 95 patients. Corneal astigmatism was measured with an automated keratometer (RK-5, Canon) and Scheimpflug tomography (Pentacam HR, Oculus). Refractive astigmatism was compared to keratometric astigmatism (based on anterior corneal measurements only), Equivalent K Reading and total corneal astigmatism (both based on anterior and posterior corneal measurements). Vector analysis was carried out by Næser’s polar value method. The accuracy was defined as the average magnitude of the vectorial difference in astigmatism (DA). Each corneal measurement was optimized in retrospect by a multiple linear regression equation between refractive and corneal astigmatism. Results: Keratometric astigmatism overestimated with-the-rule (WTR) refractive astigmatism and underestimated against-the-rule (ATR) refractive astigmatism. Several measurements based on both corneal surfaces values did not show any statistically significant difference with respect to refractive astigmatism. The mean corneal astigmatism by total corneal refractive power (TCRP) at 4.0 mm (zone/pupil) produced the lowest mean arithmetic DA and the highest percentage of eyes with a DA ≤0.50 diopter. After optimization, the accuracies of automated KA and TCRP 4.0 mm (zone/pupil) were similar. Conclusions: Total corneal astigmatism measured by the Scheimpflug tomography at 4.0 mm zone centered on pupil, accurately reflects the refractive astigmatism in pseudophakic eyes. However, the accuracy of total corneal astigmatism is not different from automated KA after optimization.

Glaucoma secondary to Peters' anomaly (PA) is an important factor affecting visual prognosis, but there are few reports on it. This study aimed to investigate the characteristics of glaucoma asso-ciated with PA and glaucoma surgery outcomes. This retrospective study included 31 eyes of 20 patients with PA. PA was classified into three stages: Stage 1, with a posterior corneal defect only; Stage 2, a corneal defect with iridocorneal adhesion; and Stage 3, a corneal defect with lens ab-normalities. The associations between glaucoma and anterior segment dysgenesis severity, visual prognosis, and glaucoma surgery outcomes were analyzed. Sixteen eyes of 10 patients developed glaucoma. Stage 1 PA had no glaucoma, 52% of Stage 2 had glaucoma, and 75% of Stage 3 had glaucoma. Of the 16 eyes with glaucoma, 11 underwent surgery. Eight of these 11 eyes achieved intraocular pressure (IOP) control. Five of the nine eyes that underwent trabeculotomy (TLO) succeeded, and none had corneal staphyloma. Three of the four eyes for which TLO was ineffective had corneal staphyloma (P=0.0331). Patients with PA are more likely to develop glaucoma as anterior segment dysgenesis progresses, and the effect of TLO is limited if corneal staphyloma is present.

Background: Cataract and Age-related Macular Degeneration are two characteristic diseases of the so-called elderly age (75-90 years and older). Both determine an important visual impairment, so it is often difficult to understand how much of the visual loss is given by the cataract opacities and how much by the degeneration of the macula and this assumes a relevant medico-legal query in clinical practice. Methods: From that pool we randomized in group 735 eyes with wAMD (males 328, females 407) Average age: 76.23±13.87 years, and in Group 819 eyes without clear signs of wAMD (males 361, females 451) Average age: was 75.88±18.21 years to randomize them we used the online randomization program (http://www.graphpad.com/quickcalcs/index.cfm) selecting random numbers and then randomly assign subjects to groups to undergo our observational study. All patients were examined with full ophtalmological visit including Best Corrected Visual Acuity (with Bailey-Lawson Chart), Anterior Segment examination, Fundus Examination, in all cases with wAMD was also performed OCT. ANOVA multifactorial statistical analysis was drawn. Results: number of patients with unsatisfactory surgery is significantly higher in the group of AMD patients, and this is easily understandable from what has been said above, but I would like to underline that in most patients there are very positive results, therefore cataract surgery is also indicated in AMD patients. Conclusions: Cataract surgery has a positive impact on the patient's life in most cases, you shouldn't be afraid to operate. However, it is necessary to find surgical measures capable of minimizing the consequences of the intervention on the retina.

Atherogenic lipoproteins may impair vascular reactivity, leading to tissue damage in various organs, including the eye. This study aimed to investigate whether ophthalmic artery reactivity is affected in mice lacking the apolipoprotein E gene (ApoE-/-), a model for hypercholesterolemia and atherosclerosis. Twelve-month-old male ApoE-/- mice and age-matched wild-type controls were used to assess vascular reactivity using videomicroscopy. Moreover, vascular mechanics, lipid content, levels of reactive oxygen species (ROS), expression of pro-oxidant redox enzymes and of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were determined in vascular tissue. Unlike the aorta, the ophthalmic artery of ApoE-/- mice developed no signs of endothelial dysfunction and no signs of excessive lipid deposition. Remarkably, levels of ROS, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NOX2, NOX4, and of LOX-1 were increased in the aorta but not in the ophthalmic artery of ApoE-/- mice. Our findings suggest that ApoE-/- mice develop endothelial dysfunction in the aorta by increased oxidative stress via involvement of LOX-1, NOX1 and NOX2, whereas NOX4 may participate in media remodeling. In contrast, the ophthalmic artery appears to be resistant to chronic apolipoprotein E deficiency. Lack of LOX-1 expression/overexpression in response to increased ox-LDL levels may be a possible mechanism of action.

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

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

To this day, use of oily eye drops and non-invasive retinal delivery remains a major challenge. Oily eye drops usually cause ocular irritation and interfere with normal function of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here the authors report a novel topical Non-Invasive Ocular Delivery Platform (NIODP) through the periorbital skin for high efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7mg JV-MD2 (omega-3 DHA) via the NIODP reached the retina at Cmax of 111µg/g and the cornea at Cmax of 66µg/g. NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to anterior segments of NHP. The topical NIODP seems to transport drug candidates through the cornea pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery, especially for oily eye drops and retinal delivery, where the success of treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue.

Age-related macular degeneration (AMD) causes visual impairment in individuals >50 years of age. However, no study has investigated AMD using ultra-wide-field swept-source optical co-herence tomography (UWF SS-OCT). We aimed to evaluate central and peripheral choroidal thickness using UWF SS-OCT and compare AMD subtypes. We included 75 eyes of patients with typical AMD (tAMD), 56 with polypoidal choroidal vasculopathy (PCV), 29 with pachychoroid neovasculopathy (PNV), and 12 with retinal angiomatous proliferation (RAP). To compare cho-roidal thicknesses in the central and peripheral choroids, we established subfields of <3 mm, <9 mm, and 9–18 mm from the fovea. PNV patients were significantly younger than those with tAMD (P=0.01). The choroidal thicknesses of PNV were significantly greater than that of tAMD in all subfields (P<0.01) and choroidal thickness significantly correlated with age and axial length in all subfields (P<0.05). Even after adjusting for age and axial length, the choroidal thickness in PNV was significantly greater than that in tAMD (P<0.05). In addition, the ratio of the posterior < 9 mm to peripheral 9–18 mm choroidal thickness in PNV was significantly greater than that in tAMD (P<0.01). A thickened choroid in PNV was more pronounced in the posterior choroid than in the periphery.

Purpose: To compare refractive prediction error (PE)s between phacotrabeculectomy and phacoemulsification. Methods: Refractive PE was defined as the difference of spherical equivalent between the predicted value using the Barrett Universal II formula and the actual value obtained at postoperative one month. Forty-eight eyes that had undergone phacotrabeculectomy (19 eyes, open-angle glaucoma; 29 eyes, angle-closure glaucoma) were matched with 48 eyes that had undergone phacoemulsification by age, average keratometry value and axial length (AL), and their PEs were compared. The factors associated with PE were analyzed by multivariable regression analyses. Results: Phacotrabeculectomy group showed a larger absolute PE compared to the phacoemulsification group (0.51 ± 0.37 Diopters vs. 0.38 ± 0.22, P=0.033). Larger absolute PE was associated with longer AL (P=0.010) and higher intraocular pressure (IOP) difference (P=0.012). Hyperopic shift (PE>0) was associated with shallower preoperative anterior chamber depth (ACD) (P=0.024) and larger IOP difference (P=0.031). In the phacotrabeculectomy group, the PE was inversely correlated with AL: long eyes showed myopic shift and short eyes hyperopic shift (P=0.002). Conclusions: Surgeons should be aware of the possibility of worse refractive outcomes when planning phacotrabeculectomy especially in eyes with high preoperative IOP, shallow ACD, and/or extreme AL.

A surgical technique aimed at rerouting aqueous humor (AH) outflow from the anterior chamber to the suprachoroidal space (SCS) without performing surgical cyclodialysis was developed to decrease intraocular pressure (IOP) in glaucoma patients. The surgical outcomes of the technique were retrospectively analyzed in fifty-eight patients. At 6, 12, and 24 months, the mean IOP decreased from 27.8±8.3 to 14.95.0 mmHg, median 15.0 (25th percentile (p25 )13.0; 75th percentile (p75) 18.0), and 15.23.3 mmHg; hypotensive medication use reduced from median (p25; p75) 3 (2; 3) to 0 (0; 2), 0 (0; 2), and 0 (0; 1.5), and complete success was achieved in 62.8%, 51.2%, and 32.5% cases, with partial success in 28.4%, 44.2%, and 62.5% cases, respectively. Eight cases (13.8%) presented unsatisfactory outcomes. Intra- and postoperative complications were few and manageable. No bleb formation was observed in any of the cases. In 50% of cases, conjunctival lymphatic vessels (CLVs) developed following surgery in superior quadrants. The technique is safe and effective in providing a long-term decrease in IOP and hypotensive medication use. It was hypothesized in this study that the IOP decrease occurred as a result of enhanced AH outflow from the SCS to CLVs through intrascleral microchannels connecting the SCS to CLVs.

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycemia. Plant-based therapies are characterized by low bioavailability in ocular tissues. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR, were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Fundus of retinal arterioles, retina histopathology and lens transmission electron microscopy (TEM), were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fiber disorganization. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately edematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA formation and increased antioxidant capacity. Retinal edema and disorganization in lens fibers were still present.

Purpose: To assess clinical outcomes of corneal cross-linking (CXL) intervention in a population diagnosed with progressive keratoconus. Methods: This single-center retrospective cohort study included consecutive patients who underwent standard CXL or accelerated CXL for progressive keratoconus at a major teaching hospital in south Israel between January 2015 and December 2019. Patient medical files were reviewed to extract demographic, clinical, and tomographic data from outpatient clinic reports before treatment and one year post-operatively. Results: This study included 166 patients (representing 198 eyes), out of which 98 patients (123 eyes) were ethnically Bedouin, and 68 patients (75 eyes) were ethnically Jewish. Overall, 126 patients (144 eyes) had a follow-up of at least 12 months (16.84±5.76). The mean patient age was 20.62 ± 7.1 years old. There were significant baseline differences between the two ethnical groups in best-corrected visual acuity (BCVA; p < 0.001), uncorrected visual acuity (UCVA; p < 0.001), mean keratometry (p = 0.028), and corneal thickness (p < 0.001). Significant changes in BCVA, UCVA, and pachymetry parameters within each group were found after 12 months. Negative binomial regression analysis showed a maximal keratometry below 55D (RR=1.247, p < 0.001) and a standard CXL procedure (RR=1.147, p = 0.041) are significantly related to the stability of KC after 12 months. However, the effect size of the origin of patients is negligible (RR=1.047, p = 0.47). Conclusions: In this study, the Bedouin population suffered from more progressive keratoconus when compared to the Jewish population. CXL was significantly effective in improving BCVA and UCVA in both groups after 12 months of follow-up.

Children with autism spectrum disorder (ASD) may have impaired vision from high refractive errors: near-sighted-myopia or far-sighted-hyperopia and aversion to spectacles or contact lenses. Refractive surgery can restore sharp vision and eliminate the need for spectacles or contact lenses. Restoration of sharp vision may improve ASD behaviors. Data were collated retrospectively for 267 children with refractive errors and neurodevelopmental disorders (NDD) diagnosed as ASD alone or NDD with ASD-like behaviors. Surgery was either laser photo-refractive keratectomy (PRK; 131 children), implantation of a phakic intra ocular lens (pIOL; 129 children) or removal of the crystalline lens and implantation of an IOL (refractive lens exchange, RLE; 21 children) under general anesthesia. Median age was 10.9 yrs. and median follow-up 3.1 yrs. Pre-operative refractive errors ranged from a mean +7.5 ± 0.9 D to -14.3. ± 4.8 D. Surgery corrected 87% to normal focal length (± 1 D). Visual acuity improved an average 0.6 logMAR. Social interactions and ASD behaviors improved in 55% (146/267) of the treated children (p &lt; .01), including school performance; motor skills; depth perception; repetitive or stereotyped movements; anxiety/fear; and attention. Refractive surgery improves both visual function and behaviors in the majority of highly near-sighted or far-sighted children with ASD.

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.

This study aimed to compare the efficacies and safety of enhanced and standard monofocal intraocular lenses (IOLs) in eyes with early glaucoma. Patients with concurrent cataracts and open-angle glaucoma (OAG) were enrolled. They underwent cataract surgery with IOL implantation. Manifest refraction; monocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), and uncorrected near visual acuity (UNVA); visual field (VF); contrast sensitivity (CS); defocus curves and questionnaires were assessed three months postoperatively. Thirty-four and 38 patients had enhanced and standard monofocal IOLs, respectively. The enhanced monofocal IOL provided better UIVA than the standard monofocal IOL (p = 0.003) but similar UDVA, CDVA and UNVA. The enhanced monofocal IOL had more consistent defocus curves than the standard monofocal IOL, especially at -1 (p = 0.042) and -1.5 (p = 0.026) diopters. The enhanced monofocal IOL provided better satisfaction (p = 0.019) and lower spectacle dependence (p = 0.004) than the standard monofocal IOL for intermediate vision, with similar VF and CS. In conclusion, the enhanced monofocal IOL is recommended for patients with OAG because they provide better intermediate vision, higher satisfaction, and lower dependence on spectacles than standard monofocal IOL, without worsening other visual outcomes.

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.

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness world-wide. We recently reported that polyethylene glycol (PEG) can activate the alternative pathway of the complement system and induce choroidal neovascularization (CNV) in mice. Currently, no other investigator has demonstrated CNV after PEG injection in the mouse eye. The aim of this article is twofold: we review the histologic changes in mouse retina and retinal pigmented epithelium (RPE) after treatment with PEG, and we summarize a model of wet and dry AMD pathogenesis in mice through subretinal PEG treatment of RPE cells and retinal layers. We injected (subretinal) male C57BL/6 mice with 2 μL of solution containing 0.5 mg and 1.0 mg of PEG or PBS in control groups. Eyes were harvested at day 1, 3 and 5 after injection and processed for analysis. Sections were immunohistochemically stained for complement component C3, mem-brane attack complex (MAC), and cytokeratin 18. Light and laser confocal microscopy was used for image capturing. PEG increased deposition of C3 and MAC on RPE cells and on all retinal layers after 1.0 mg injection. PEG induced loss of cellular contacts between RPE cells and migration of RPE cells in the subretinal space at day 1 after PEG injection. After 0.5 mg PEG injection, increased size of RPE cells was detected at day 3 and 5. Apoptotic bodies were observed in outer nuclear layer at day 3 and 5 after 0.5 mg PEG treatment. RPE cells with dark cytoplasm and condensed chromatin were observed. Higher doses of PEG induce CNV, encouraged RPE cell proliferation and death, and damage photoreceptors in mice. This simple and fast model may be useful to explore the pathogenesis of both dry and wet AMD.

Glaucoma, a group of diseases characterized by progressive retinal ganglion cell loss, cupping of the optic disc and by a typical pattern of visual field defects, is a leading cause of severe visual impairment and blindness worldwide. Elevated intraocular pressure (IOP) is the leading risk factor for glaucoma development. However, glaucoma can also develop at normal pressure levels. An increased susceptibility of retinal ganglion cells to IOP, systemic vascular dysregulation, endothelial dysfunction and autoimmune imbalances have been suggested to play a role in the pathophysiology of normal tension glaucoma. Since inflammation and oxidative stress play a role in all forms of glaucoma, the goal of this review article is to resent an overview on the inflammatory and prooxidant mechanisms in the pathophysiology of glaucoma and to discuss immunomodulatory and antioxidant treatment approaches.

Background: We compared corneal visualization Scheimpflug technology (CST) parameters between eyes with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Methods: A retrospective analysis was done on data from 89 eyes with POAG and 83 eyes with PACG that had CST examinations. CST parameters were compared between eyes with POAG and those with PACG using a linear mixed model (LMM). Results: No differences were observed in age, central corneal thickness, intraocular pressure, or use of antiglaucoma eye drops between the two groups. Patients with PACG had a significantly shorter axial length (AL), a higher proportion of females, CST parameters, longer applanation 2 (A2) time, deeper A2 deformation amplitude, shorter peak distance (PD), longer whole eye movement, and longer whole eye movement time than patients with POAG. Highest concavity (HC) length and PD showed a significant positive correlation with AL. However, A1 length, A1 deformation amplitude, A2 time, A2 velocity, A2 length, A2 deformation amplitude, HC time, whole eye movement, and whole eye movement time were negatively correlated with AL. Conclusions: Biomechanical properties of the cornea differed between PACG and POAG. In some parts, AL differences between the POAG and PACG groups might contribute to the variation in CST parameters.

Background: To examine the effects of continuous positive airway pressure (CPAP) therapy on central corneal thickness (CCT) in patients with obstructive sleep apnea (OSA) followed for 12 months. Methods: Participants were patients with OSA and an indication for CPAP who were enrolled after diagnosis and graded according to the apnea hypopnea index (AHI) determined in an overnight polysomnography. Each subject underwent a full ophthalmologic examination including ultrasound pachymetry (USP) with an SP3000 USP (Tomey Inc) at the time points just before CPAP onset, and after 3 and 12 months of CPAP treatment. Results: The study sample comprised 40 eyes of 20 patients. Adherence to CPAP was adequate (5.23 ± 1.77 h/night). After receiving 12 months of CPAP, positive correlation was observed between hours of CPAP use and CCT (r = 0.382, p = 0.015). Intermittent hypoxemia pre-CPAP or hypoxia severity pre-CPAP were also positively correlated with the CCT recorded after 12 months of CPAP (r = 0.394, p = 0.012; r = 0.324, p = 0.041). Significant correlations were, however, not observed after only 3 months of CPAP treatment. In addition, compared to measurements at 3 months, intraocular pressure was higher after 12 months of treatment. Conclusions: Our findings indicate that 12 months of correct adherence to CPAP are needed to detect significant CCT thickening, and that the greater the pre-CPAP hypoxemia, the greater the capacity for an increase in CCT to be produced in response to 12 months of this therapy.

Background: With the increasing global incidence of diabetes mellitus (DM), diabetic retinopathy (DR) has become one of the leading causes of blindness in developed countries. DR leads to changes in retinal neurons and microcirculation. Rtx1TM (Imagine Eyes, France) is a microscope that allows histological visualisations of cones and retinal microcirculation throughout the DM duration. Objective: This study aimed to analyse the cones and retinal microvascular changes in 50 diabetic individuals and 18 healthy volunteers. The patients participated in the initial visit and two fol-low-up appointments: one and two years after the study, beginning with rtx1 image acquisition, visual acuity assessment, macular OCT scans and blood measurements. Results: The study revealed significant differences in the cone density, mosaic arrangement and vascular morphology between healthy and diabetic patients. The final measurements have shown decreased photoreceptor and microvascular parameters in the DR group compared to the control group. Furthermore, in the 2-year follow-up, both groups' rtx1-acquired morphological changes were statistically significant. Conclusions: Rtx-1 technology was successfully used as a non-invasive method of photoreceptors and retinal vasculature assessment over time in patients with diabetic retinopathy. The study has revealed a trend toward more vascular morphological changes occurring over time in diabetic patients.

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.

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber's hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies.

Purpose: This research compared the dissociated phoria at near and distance fixation in free space using three techniques: the Howell test, alternate Cover test, and Thorington test. Methods: 220 healthy Mexican children (age 5.06-17.11) participated in this study. Phorias were quantified at both distances using each test, from the least to the most disruptive. The stereopsis degree and near point of convergence (break/recovery) were analyzed to understand their role on the visual system's sensorimotor balance. Results: For the exophoria/esophoria at near, the alternate Cover and Thorington tests showed similar values. The exophoria at distance, was similar with the alternate Cover and Howell tests, while esophoria, with the alternate Cover and Thorington tests. The break value and near exophoria relates to each other and affect the stereopsis degree, whereas age is associated with the stereopsis degree and break value. Conclusions: The analysis revealed that alternate Cover and Thorington tests can substitute one another, but not with the Howell test. The test's specific dissociation method may explain these results. Analyzing the binocular visual system provides information about its sensorimotor balance and fragility when faced to the technique’s degree of dissociation.

The purpose of this study was to describe ocular surface and anterior eye segment findings in various types of ichthyoses. Methods: This was a single-center prospective observational study. The study group consisted of five patients (P1-P5) aged 13–66 years. Multimodal imaging was performed, including slit-lamp examination, swept-source optical coherence tomography (SS-OCT), and in vivo confocal microscopy (IVCM). Results: All patients were diagnosed with moderate to severe dry eye disease (DED). Corneas showed a significant pattern of irregularity, with a significant difference between the corneal thickness at the apex (CAT) and corneal thinnest thickness (CTT), ranging from 5 to 375 µm. Three patients were diagnosed with ectasia patterns based on SS-OCT. All patients showed abnormalities in at least one Fourier index parameter for at least one eye at 3 or 6 mm, on keratometric, anterior, or posterior analyses. IVCM examination revealed changes in all corneal layers. Conclusions: By combining the results of multimodal im-aging, we were able to detect preclinical abnormalities, distinguish characteristic changes com-mon to ichthyosis, and reveal the depth and characteristics of corneal abnormalities. Therefore, patients with ichthyosis should be examined for DED and ectatic disorders early in clinical prac-tice.

Pars plana vitrectomy is today a common first-line procedure for treatment of rhegma-togenous retinal detachment (RRD). Removal or preservation of the natural lens at the time of vitrectomy is associated with both advantages and disadvantages. The combi-nation of cataract extraction (i.e., phacoemulsification) with pars plana vitrectomy (PPVc) enhances visualization of the peripheral retina and the surgical management of the vitreous base. However, PPVc prolongs the surgical time and is associated with iatrogenic loss of the accommodation function in younger patients, possible postoperative aniso-metropia, and unexpected refractive results. Performance of pars plana vitrectomy alone (PPVa) requires good technical skills to minimize the risk of lens damage, and quickens cataract development. We retrieved all recent papers that directly compared PPVc and PPVa using parameters that we consider essential when choosing between the two procedures (the success rate of anatomical RRD repair, postoperative refractive error, intra and postoperative complications, and costs). PPVa and PPVc were generally comparable in terms of RRD anatomical repair. PPVc was associated with fewer intraoperative, but more postoperative, complications. Macula-off RRD PPVc treatment was often associated with undesirable myopic refractive error. PPVa followed by phacoemulsification was the most expensive procedure.

Hereditary hemochromatosis (HH) is an inherited iron metabolism disorder. It is caused by an autosomal recessive disorder resulting from a C28Y8 HFE gene mutation. Mutations in the HFE gene may result in iron accumulation and oxidative stress in the retina, resulting in macular degeneration. This article describes two patients with HH who developed vision difficulties. Both patients were subjected to a retinal exam, multimodal imaging, and electrodiagnostic techniques, which revealed structural and functional degeneration of the central macula. Fundus photography, fluorescein angiography (FA), and fundus autofluorescence (FAF) revealed changes at the level of the retinal pigment epithelium (RPE) in the center of the macula, while optical coherence tomography (OCT) revealed subfoveal accumulation of hyperreflective material at and below the RPE. The multifocal electroretinogram (mfERG) confirmed a decreased cone response, whereas the full-field electroretinogram (ERG) revealed no pathological findings. In addition, patients underwent genetic testing, which ruled out the possibility of hereditary macular dystrophy. Considering macula findings and the nature of the patients' primary illness, we believe that the higher concentration and accumulation of iron and photoreceptor metabolic products have led to dysfunction in the RPE, which has led to morphological and functional changes in the macula.

Purpose: To report the progression of patients diagnosed with birdshot chorioretinopathy (BSCR) initially treated with corticosteroids. Methods: We included 39 BSCR patients followed for ≥1 year. Patients were classified into 2 groups according to their initial treatment: methylprednisolone followed by prednisone (n=28) and prednisone alone (n=11). We analyzed the progression under treatment after 1, 3, 6 months, 1 year, and at the end of follow-up. Results: At the end of follow-up, 31/39 (79.5%) patients had reached inflammation control. Thirteen out of 28 (46.4%) and 6/11 (54.5%) patients were treated exclusively with corticosteroids, and 18/19 (94.7%) of them had reached inflammation control at the end of follow-up; their mean (range) corticosteroid dose was 3.5 (0-10) mg/day. Conclusion: We found that the prolonged corticosteroid therapy treatment strategy resulted in inflammation control in half of BSCR patients. This control was maintained with low doses of cortisone, usually <5 mg/day.

The early failure of glaucoma surgery is mainly caused by an overly fibrosis at the subconjunctival space causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signature with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of VEGF-A, IL-8, C-MYC, and CDKN1A was induced in the conjunctiva of hyperfibrosis patients. VEGF-A and IL-8 protein levels were also increased in fibroblast supernatants. We propose that these proteins may act as biomarkers of conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery leading to more optimal and personalized treatments.

The XEN® gel stent reduces intraocular pressure (IOP) in glaucoma. XEN®-45 is widely used while the newer XEN®-63 has a larger lumen that may lower IOP more. We retrospectively compared the first 15 XEN®-63 cases to 15 matched XEN®-45 controls. With a preoperative IOP of 18.1 ± 3.9 mmHg (mean ± SD) and a final IOP of 9.2 ± 4.2 mmHg, XEN®-63 implantation resulted in an IOP reduction of 48.0 ± 23.3%. Similarly, with a preoperative IOP of 18.3 ± 4.5 mmHg and a final IOP of 10.5 ± 2.3 mmHg, XEN®-45 implantation resulted in an IOP reduction of 39.5 ± 17.81%. The median follow-up period was 57 days for the XEN®-63 group and 183 days for the XEN®-45 group. 5/15 eyes of each group underwent open conjunctival bleb revision within the period of observation. Two eyes of the XEN®-63 group also had secondary glaucoma surgery. In both groups only one eye required restart of antiglaucomatous medication. XEN®-63 and XEN®-45 effectively lower IOP and medication. XEN-63 achieved lower IOP over a short follow-up. Com-plication and revision rates were similar.

Neovascular age-related macular degeneration (nAMD) leads to visual impairment if not treated timely. Intravitreal anti-VEGF drugs have revolutionized nAMD treatment in two decades. We evaluated visual outcomes of anti-VEGF treatment in nAMD. A real-life population-based cohort study. Data included parameters for age, sex, age at the diagnosis, laterality, chronicity, symptoms, visual outcomes, lens status, and history of intravitreal injections. A total of 1088 eyes (827 patients) with nAMD were included. Visual acuity was stable or improved in 984 eyes (90%) after an average 36±25 months follow-up. Bevacitzumab was the first-line drug in 1083 (99.5%) eyes. Vision improved ≥15 ETDRS letters in 377 (35%), > 5 ETDRS letters in 309 (28%) and was stable (±5 ETDRS letters) in 298 (27%) eyes after anti-VEGF treatment. The loss of 5-<15 ETDRS letters in 44 (4%) and ≥15 ETDRS letters in 60 (6%) eyes was noted. At the diagnosis of nAMD, 110 out of 827 patients (13%) fulfilled the criteria of visual impairment, whereas 179 patients (22%) were visually impaired after the follow-up. Improvement or stabilization in vision was noted in 90% of the anti-VEGF-treated eyes with nAMD. In addition, anti-VEGF agents are crucial in diminishing nAMD-related visual impairment.

: 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.

The purpose of the study was to determine the “retinal thickness deviation” (RTD) in diabetic macular edema (DME) eyes treated with intravitreal therapy and to establish associations be-tween RTD and best-corrected visual acuity (BCVA). We conducted a retrospective study, in-cluding consecutive DME eyes undergoing intravitreal therapy with two years of follow-up. BCVA and central subfield thickness (CST) were collected at baseline, 12 months and 24 months of follow-up. RTD was calculated as the absolute difference between measured and normative CST values at each time point. Linear regression analyses were performed between RTD and BCVA and between CST and BCVA. One hundred and four eyes were included in the analysis. The RTD was 177.0 (117.2) μm at baseline, 97.0 (99.7) μm at 12 months and 89.9 (75.3) μm at 24 months of follow-up (P < .001). RTD showed a moderate association with BCVA at baseline (R2=0.134, p<0.001) and 12 months (R2=0.197, p<0.001), and a substantial association at 24 months (R2=0.272, p<0.001). The CST showed a moderate association with BCVA at baseline (R2=0.132, p<0.001) and 12 months (R2=0.136, p<0.001), while the association was weak at 24 months (R2=0.065, p=0.009). In conclusion, RTD showed a good association with visual outcome in DME eyes undergoing intravitreal treatment.

Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) is a well-known inflammatory, neurovascular complication of diabetes and a leading cause of preventable blindness in developed countries among working-age adults. However, the ocular surface components of diabetic eyes are also at risk of damage due to uncontrolled diabetes, which is often overlooked. Inflammatory changes in the corneas of diabetic patients indicate that inflammation plays a significant role in diabetic complications, much like in DR. The eye´s immune privilege restricts immune and inflammatory responses, and the cornea and retina have a complex network of innate immune cells that maintain immune homeostasis. Nevertheless, low-grade inflammation in diabetes contributes to immune dysregulation. This article aims to provide an overview and discussion of how diabetes affects the ocular immune system’s main components, immune-competent cells, and inflammatory mediators. By understanding these effects, potential interventions and treatments may be developed to improve the ocular health of diabetic patients.

Oxidative stress (OS) is involved in the pathogenesis of retinal neurodegenerative diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) and an important target of therapeutic treatments. New therapeutics are tested in vivo despite limits in transferability and ethical concerns. Retina cultures using human tissue can deliver critical information and significantly reduce the number of animal experiments along with increased transferability. We cultured up to 32 retina samples derived from one eye, analyzed models’ quality, induced OS, and tested efficiency of antioxidative therapeutics. Bovine, porcine, rat, and human retinae were cultured in different experimental settings for 3-14 d. OS was induced by high-glucose or hydrogen peroxide (H2O2) and treated by Scutellarin, pigment epithelium-derived factor (PEDF), and/or granulocyte macrophage-colony stimulating factor (GM-CSF). Tissue morphology, cell viability, inflammation, and glutathione level were determined. Retina samples showed only moderate necrosis (23.83±5.05 increased to 27.00±1.66 AU PI-staining over 14 d) after 14 days in culture. OS was successfully induced (reduced ATP content of 288.3±59.9 vs. 435.7±166.8 nM ATP in controls); antioxidants reduced OS-induced apoptosis (from 124.20±51.09 to 60.80±319.66 cells/image after scutellarin-treatment). Enhanced mammalian animal and human retina cultures allow reliable, highly transferable research on OS-triggered age-related diseases and pre-clinical testing during drug development.

Seasonal changes and varying degree of corneal hydration has been linked to excimer laser corneal ablation rates. Use of PMMA as calibration material in refractive lasers is well established. However, PMMA ablation may be equally affected by seasonal variations in temperature and humidity, intern affecting the calibration process. Aim of this work is to analyze the effect of seasonal changes in PMMA Performance using SCHWIND AMARIS laser system. PET and PMMA ablations conducted in climate-controlled environment with 826 consecutive AMARIS systems manufactured over 6 years were retrospectively analyzed. Lasers were stratified depending on seasons and months of the year. Metrics like Single laser pulse fluence, nominal number of laser pulses, mean performance, standard deviation, and technical performance of system were compared to global average values. Cyclic winter-summer variation was confirmed with seasons winter and summer showing statistically significant variations with respect to global values. Metric technical performance showed deeper PMMA ablation performance in summertime, with maximum seasonal deviation of 6%. Results were consistently confirmed in seasonal as well as monthly analyses. These findings could help minimize variance among laser systems by implementing compensation factors depending on seasons such that laser systems installed worldwide follow the same trend line of variation.

A clinical case of atypical endophthalmitis in an 82-year-old patient who underwent complicated cataract phacoemulsification. Clinical manifestations showed signs of a bacterial process, however, the treatment was not effective. Antifungal therapy had yielded positive results, despite the low probability of a fungal etiology of the process.

Uveal melanoma represents the most prevalent form of primary malignant intraocular tumor in adults. Historically, enucleation was considered the gold-standard approach in the treatment of uveal melanoma. Nowadays, radiotherapy is the most commonly used therapy, aiming at a better quality of life. However, radiotherapy can result in several ocular complications, some of which may be vision-threatening. Radiation-induced dry eye, scleral necrosis, cataract, rubeosis iridis, neovascular glaucoma, radiation retinopathy and maculopathy and optic neuropathy are the most common. This article aims to summarize the current literature on the ocular complications after radiotherapy, their clinical features, risk factors and management strategies. A thorough understanding is crucial for ophthalmologists and oncologists to provide optimal patient care, improve visual outcomes, and minimize long-term complications.

Background: this retrospective study aimed to analyze the results of the combination of the Haigis formula and Total Keratometry (TK) to calculate the IOL power in eyes with previous corneal refractive surgery. Methods: The TK value provided by the IOL Master 700 (Carl Zeiss Meditec) was introduced into the Haigis formula; the mean prediction error (PE), mean absolute error (MAE), median absolute error (MedAE) and percentage of eyes with a PE within ±0.25 D, ±0.5 D, ±0.75 D and ±1.00 D were calculated. Results: Ninety-three eyes of 93 patients with previous laser refractive surgery were evaluated. Two groups were defined: Group A included 51 previously myopic eyes, Group B included 42 previously hyperopic eyes. The mean PE in Group A was +0.09 ±0.44 D and 76.47% of eyes had a PE within ±0.50 D. In Group B the mean PE was -0.15 ±0.46 D and 66.67% of eyes had a PE within ±0.50 D. Discussion: The Haigis formula combined with TK is one of the most accurate available methods for IOL power calculation in eyes with prior myopic and hyperopic corneal refractive surgery. In such eyes the results are similar to or better than those reported in previous studies.

We have established earlier a cell line from the human limbal area to study cell growth and response to the toxic effects of antibiotics used in ophthalmology. In the recent work, the effect of multi-walled carbon nanotubes (MWCNTs) in cornea damage was investigated in vitro and in vivo in mice. In the in vitro experiments, the physiological effects of multi-walled carbon nano-tube (MWCNT) bundles on corneal wound healing were mimicked in vitro by a reepithelization limbal stem cell model. Murine in vivo experiments were performed with intact, non-functionalized MWCNTs to confirm the validity of in vitro tests. The MWCNTs of 10 -30 nm outer diameter at low concentration (5 µg/ml) did not interfere with the wound healing of the damaged limbal cell monolayer. Higher than 50 µg/ml concentrations: a) generated MWCNT aggregates, b) restrained the movement and prolonged the time of wound healing, c) increased the amplitudes of the oscillations of the cells, and d) resulted in scar formation affecting both cor-neal function and refraction. Chromatin condensation, a sensitive test of the viability of cells, including limbal stem cells revealed that the presence of a low concentration of nanotubes (5 µg/ml), did not significantly affect the viability of limbal cells. Chromatin condensation was completed and metaphase chromosomes were seen at higher MWCNT concentration proving that their aggregates did not affect the viability of limbal cells. This concentration of MWCNTs (5 µg/ml) did impact neither the reepithelization in vitro nor in vivo in the scratched eyes of mice. Scar formation took place at higher than 50 µg/ml concentrations and the healing of the cornea was prevented by the lack of movement of increasingly larger macroaggregates. In vivo murine experiments vali-dated in vitro monolayer regrowth followed by time-lapse microscopy portraying realistically the reepithelization of the damaged cornea that process was gradually slowed down by macro aggregate formation and caused the scarring of the cornea.

Assessing corneal biomechanics in vivo has long been a challenge in the field of ophthalmology. Although recent wave-based optical coherence elastography (OCE) methods have shown promise in this area, the effect of intraocular pressure (IOP) on mechanical wave propagation in the cornea remains unclear. To address this, we constructed an artificial eye model and performed surface wave OCE measurements in the radial directions (54–324°) of the silicone cornea at varying IOP levels (10–40 mmHg). The results demonstrated increases in wave propagation speeds (mean ± STD) from 6.55 ± 0.09 m/s (10 mmHg) to 9.82 ± 0.19 m/s (40 mmHg), leading to an estimate of Young’s modulus, which increased exponentially from 145.23 ± 4.43 kPa to 326.44 ± 13.30 kPa. Our implementation of an artificial eye model highlighted that the impact of IOP on Young’s modulus (ΔE = 165.59 kPa, IOP: 10–40 mmHg) was more significant than the effect of stretching of the silicone cornea (ΔE = 15.79 kPa, relative elongation: 0.98%–6.49%). Our study sheds light on the potential of using an artificial eye model in OCE research for corneal biomechanics. Furthermore, it is critical to consider the impact of IOP on measurement results when utilizing wave-based OCE in clinical settings for enhanced assessment of corneal biomechanics.

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.

Corneal opacity is a leading cause of vision impairment and suffering worldwide. Transplantation can effectively restore vision and reduce chronic discomfort. However, there is a considerable shortage of viable corneal graft tissues. Tissue engineering may address this issue by advancing xeno- keratoplasty as a viable alternative to conventional keratoplasty. In particular, livestock decellularization strategies offer the potential to generate bioartificial ocular prosthetics in sufficient supply to match existing and projected needs. To this end, we have examined the best practices and characterizations that have supported the current state-of-the-art driving preclinical and clinical applications. Identifying the challenges that delimit activities to supplement the donor corneal pool derived from acellular scaffolds allowed us to hypothesize a model for keratoprosthesis applications derived from livestock combining 3D printing and decellularization.

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.

After long years of development, the technology of analyzing the working condition of power units based on vibration signals has had relatively stable applications, but the accuracy and the degree of automation and intelligence for fault diagnosis are still inadequate due to the limitations of the current development of key technologies. With the development of big data and artificial intelligence technology, the involvement of new technologies will be an important boost to the development of this field. To support the subsequent research, bibliometrics is used as a tool to sort out the development of the technology in this field at the macro level; at the micro level, the classical and key literature is studied to grasp the development status at the technical level and prepare for the selection of entry points to continue in-depth innovation afterwards.

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.

The cornea is an avascular tissue which has attracted much attention by the uniqueness of its anatomical characteristics, it has, in proportion, an enormous size, in relation to the number of vessels, because on average few cells in the organism are away more than 30 microns of a blood vessel. However, the cornea, with a diameter of between 11 and 12 mm, is a unique example. It has been tried to explain the notable absence of blood vessels in the cornea, arguing that corneal tissues are able to take oxygen directly from the air. In this article we are explaining that based on the physicochemical characteristics of molecular oxygen and the cell membrane, cytoplasm, water, and cellular metabolism, it is not possible that epithelial corneal cells directly take oxygen from the air, instead, corneal cells have molecules that can dissociate the water molecules thereby these cells, like any other eukaryotic cells, take the oxygen from the intracell water, like plants.

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.

Aim: This study measures and evaluates the socioeconomic burden of people living with keratoconus in Saudi Arabia. Methods: The study employed a cross-sectional design, a Keratoconus Economic Burden Questionnaire, and a convenient sample of 89 keratoconus patients (58.4% male) drawn from multiple regions in Saudi Arabia. It was conducted using online surveys and the data was analysed using appropriate quantitative techniques. Results: The mean age and annual income of participants were 33.24 years and Saudi Riyal (SAR) 33,505.6180 (SD=62,215.29), respectively, with only 37% being employed for wages. Up to 94.4% needed glasses or contact lenses at least once a week and 73.0% received care from optometrists. The condition forced 45.9% of the respondents to change careers or leisure activities, with a further 51.3% having to take time off work. The mean annual out-of-pocket expenses for buying and maintaining glasses or contact lenses as well as traveling and accommodation for keratoconus-related treatment were SAR 8,673.19 (SD=11,307.73), with 48.32 incurring upwards of SAR 12,000 over the period. The treatment costs increased with disease duration, r(89) = .216, p < .05. Regression results show that the existence of comorbid eye disease, changing glasses at least once a year, and wearing either glasses or contact lenses at least once a week individually have statistically significant, negative effects on the total annual keratoconus treatment costs, while disease duration, utilisation of optometrists, and taking time off had a statistically significant increase on the total cost (p<.05). Conclusion: With a prevalence rate of 1 in 375, progressive debilitation, and the lifetime nature of the disease, keratoconus is a critical public health concern in Saudi Arabia. The resulting visual impairment and discomfort as well as both direct and indirect economic burdens have considerable impacts on the patient's quality of life.

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.

Lacrimal Gland Prolapse is an important diagnosis to exclude in patients presenting with lateral upper eyelid fullness. Prolapse of the lacrimal gland is the descend of the lacrimal gland into the anterior orbit. It could be responsible for blepharoptosis and unattractive appearance. This is a case report of a young patient with lacrimal gland prolapse who has been treated by repositioning with suture in an outpatient surgical setting.

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.

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.

Glaucomatous optic neuropathy, a major cause of blindness, is characterized by the loss of retinal gan-glion cells (RGCs) and degeneration of their axons. Mitochondria are deeply involved in maintaining RGCs and their axons. Therefore, lots of attempts have been made to develop diagnostic tools and therapies tar-geting mitochondria. Recently, we reported that mitochondria are uniformly distributed in unmyelinated axons of RGCs, possibly owing to the ATP gradient. Thus, using transgenic mice expressing yellow fluo-rescent protein targeting mitochondria exclusively in RGCs within the retina, we assessed the alteration of mitochondrial distributions induced by optic nerve crush (ONC) via in vitro flat-mount retinal sections and in vivo fundus images captured through the cornea with a confocal scanning ophthalmoscope. We observed that the mitochondrial distribution in unmyelinated axons of RGCs that survived the ONC remained uni-form, although their density increased. Furthermore, via in vitro analysis, we discovered that the mitochon-drial size is attenuated following ONC. These results suggest that ONC induces mitochondrial fission without disrupting the uniform mitochondrial distribution. This mechanism may help to prevent axonal degeneration and apoptosis. The in vivo visualization system of axonal mitochondria in RGCs may be ap-plicable in the diagnosis of progression of optic neuropathy.

Inherited retinal dystrophies (IRDs) are a global problem that is largely unaddressed, especially in Africa. Black indigenous Africans are rarely represented in research that develop genetic tests and genetic therapies for IRDs yet their genomes are more diverse. The aim of this literature review is to synthesize information on the IRD genetic research conducted among indigenous black Africans to identify challenges and opportunities for progress. PubMed was searched to identify empirical publications reporting the genetic analysis of IRDs among indigenous Africans. A total of 10 articles were selected for the review. Based on the information in the articles, the main genetic testing methods in use include next-generation, whole exome, and Sanger sequencing. The main IRDs characterized by the genetic tests include retinitis pigmentosa, Leber Congenital Amaurosis, Stagardt disease, and cone dystrophy. Examples of implicated genes include MERTK, GUCY2D, ABCA4, and KCNV2 for the four IRDs respectively. Research activities on the genetics of IRDs are generally scanty in Africa. Even in South Africa and North Africa where some research activities were noted, only a few indigenous black Africans were in the study cohorts. There is an urgent need for genetic research on IRDs, especially in East, Central, and West Africa.

(Background) the aim was to determine related factors to recurrent vitreous hemorrhage (RVH) in a sample of proliferative diabetic retinopathy (PDR) patients. (Methods) A retrospective, review-based study. We studied 183 eyes from 121 type 2 diabetes patients with PDR. We recorded diabetes duration, history of hypertension, retinal photocoagulation status, the posterior vitreous status, the mean HbA1c, mean hemoglobin, the renal function, and the systemic complications related to diabetes. We also recorded the use of ranibizumab prior to vitrectomy and the following surgical variables: the application of segmentation and diathermy on fibrovascular proliferative tissue, the use of silicone oil, and the occurrence of surgical complications, to study which independent variables were significantly related to the presence of RVH. (Results) Duration of diabetes (P= 0.028), hemoglobin (P=0.02), status of the posterior vitreous (P=0.03), retinal photocoagulation (P=0.002) and use of segmentation surgery technique (P=0.003) have significant link to the presence of RVH. In addition, patients with diabetic polyneuropathy, myocardial infarction and ischemia in lower limbs had more vitreous hemorrhage events (p&lt;0.001). (Conclusions) Patients with PDR and with longer diabetes duration, anemia, attached posterior vitreous, deficient retinal photocoagulation, and previously cardiovascular events, were more prone to RVH.

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.

(1) Background: Diabetic retinopathy (DR) is a complication of diabetes mellitus (DM) and the COVID-19 pandemic has affected screening programmes. The aim of present study was to determine the impact of the COVID-19 pandemic on the screening of diabetes patients in our Health Care Area (HCA); (2) Methods: A retrospective study of patients with DM who had attended the DR screening programme between January 2015 and June 2022. We studied attendance, DM metabolic control and DR incidence. (3) Results: Screening for DR decreased in the first months of the pandemic. Incidence of mild and moderate DR remained stable throughout the study, and we observed a little increase in severe-DR, proliferative-DR and neovascular glaucoma, during 2021 and 2022. (4) Conclusions: The COVID-19 pandemic caused a reduction in the number of patients screened for DM, although its effect on DR seems limited, with a similar number of patients with DR throughout 2015 to 2022, despite the number of patients with severe-DR and proliferative-DR increased in 2021 and 2022.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease defined as exocrine gland hypofunction resulting in dry eyes and dry mouth. Recent interest in biological therapies for pSS has been garnered, however achieving FDA-approval has been challenging due to the numerous complications in the trials. Current literature lacks insight and a molecular target-based approach to the development of biological therapies. This review focuses on novel research in newly defined drug targets and latest clinical trials for pSS treatment. A literature search was conducted on ClinicalTrials.gov using the search term “Primary Sjögren's syndrome”. Articles published between 2000 and 2021 in English language were included. Our findings revealed the potential targets for pSS treatment in clinical trials and the most recent advances in understand-ing of molecular mechanisms underlying the pathogenesis of pSS. A prominent gap in current trials is overlooking the treatment of extraglandular symptoms such as fatigue, depression and anxiety which pervade most patients with pSS. Based on dryness and these symptom-directed therapies, emerging biological agents targeting inflammatory cytokines, signal pathways and immune reaction have been studied and proved the efficacy and safety. Novel therapies may complement existing non-pharmacological methods of alleviating symptoms of pSS. Better grad-ing systems adding extraglandular symptoms to gauge disease activity and severity should be created. The future of pSS therapies may lie in gene therapy, stem cell and tissue engineering ther-apy.

Using the OCT platform, we can generate high-resolution data on retinal nerve fiber layer (RNFL) thickness in a given eye at a large number of angular-points defined on a circular coordinate system. However, insightful characteristics of OCT RNFL data such as its circularity and granularity generally remain unutilized in its common downstream statistical analyses. We present a new circular statistical framework that defines an Angular Decay function and thereby provides a directional representation of an eye in terms of its focused RNFL loss. By applying to a clinical cohort of Asian Indian eyes, the generated circular data was modeled with a finite mixture of von Mises distributions, which led to unsupervised identification in different age-groups of 2 recurrent clusters of glaucomatous eyes with distinct directional signatures of RNFL decay. New indices of global and local RNFL loss were computed for comparing the structural differences between these glaucoma clusters across the age-groups.

(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.

Abstract Aim of the study: Presentation of ophthalmic symptoms of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infracts and Leucoencephalopathy (CADASIL). Material and methods: Clinical presentation of female patient with diagnosed CADASIL, manifested by transient loss of vision, migraine, convergence insufficiency, diplopia, increased deep tendon reflexes of upper left limb, subcortical infarcts, mood disturbances and dementia. Results: Confirmed NOTCH3 gene mutation (p.Cys212Gly), and presence of granular osmiophilic material (GOM) in cutaneous small vessel wall in immunohistochemistry laboratory test (IHC). Magnetic resonance imaging (MRI) revealed bilateral focal vasogenic lesions in white matter of cerebral hemisphere with single micro-focal infarct in the left external capsule. Furthermore, a left eye exophoria, a bilateral peripheral visual field loss of 20 degrees and a loss of nasolabial fold was confirmed during ophthalmic tests. An eye fundus examination as well as a fluorescein angiography (FA) revealed vessel constriction of retinal arteries and a peripheral retinal pigment epithelium (RPE) atrophy with focal drusen in the left eye. The doppler ultrasonography (USG) confirmed a decreased blood flow and an increased vascular resistance of the extraocular vessels. The pattern electroretinogram (PERG) revealed a reduced P50 wave amplitude in the patient’s left eye. Conclusions: intermittent blindness, migraine, convergence failure, diplopia with specific MRI signs, NOTCH3 mutation, and the presence of GOM in the skin of small blood vessels in a young or middle-aged patient suggests CADASIL. New observations include: atrophic changes in the RPE, hemodynamic disturbances in blood flow in the short posterior ciliary arteries and in the central retinal artery, single drusen in the retina, and a reduced amplitude of the P50 wave in PERG.

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.

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: 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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

(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.

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.