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A female patient in her late 70s underwent uncomplicated non-penetrating deep sclerectomy surgery. Three years after surgery, she presented with a sudden decrease in visual acuity, intraocular pressure (IOP) of 2 mmHg, macular folding and significant macular subretinal fluid. Assuming hypotony as the cause, topical dexamethasone was started, with complete functional and imagological improvement. Two months after withdrawal, she returned with the same symptoms and imagological findings. The same topical treatment was re-established, with progressive and complete improvement. After 14 months of follow-up and a maintenance dose of topical dexamethasone (1id), the patient remained stable with an IOP of 16 mm Hg. Hypotony maculopathy can, in rare cases, lead to subretinal fluid and neurosensory detachment. Topical corticosteroids can reverse and prevent hypotony in patients who are corticosteroid responsive. In advanced glaucoma, extremely low IOP may be as dangerous as high IOP. Timely normalisation of IOP may restore normal retinal architecture with associated functional improvement.

A man in his 60s presented with a subacute paracentral scotoma and preserved visual acuity in the left eye. He was found to have a very subtle area of deep retinal whitening at the macula and multiple retinal cholesterol emboli. Optical coherence tomography (OCT) with En face imaging revealed globular paracentral acute middle maculopathy (PAMM). A diagnosis of PAMM associated with branch artery occlusion was made and the patient was immediately transferred to the nearest stroke centre. Investigations revealed severe carotid occlusive disease for which the patient underwent carotid endarterectomy. Paracentral scotomas in patients with little clinical findings on fundus examination should raise the suspicion for PAMM, which is easily identifiable on OCT. Eye care professionals must recognise PAMM as a possible sign of acute retinal arterial ischaemia—an ocular and systemic emergency that requires immediate referral to specialised stroke centres.

A male patient presented with a sudden visual decline in the right eye (OD). Fundus revealed bilateral vasculitis; OD also showed an occluded inferior retinal vein and a wedge-shaped retinal opacification of the inferior macula and nasal retina. Fluorescein angiography revealed occlusive retinal vasculitis, while optical coherence tomography showed paracentral acute middle maculopathy (PAMM) in the OD. A thorough systemic evaluation revealed hyperhomocysteinemia and a positive Mantoux test. A diagnosis of PAMM with occlusive retinal vasculitis in presumed intraocular tuberculosis and hyperhomocysteinemia was made. Retinal vasculitis improved with oral corticosteroid, intravitreal anti-vascular endothelial growth factor and laser photocoagulation. However, the patient declined antitubercular therapy despite recommendations. This unique report indicates that PAMM may complicate tubercular retinal vasculitis, especially in the presence of systemic hypercoagulable states.

A woman in her 70s who was being followed up for neovascular age-related macular degeneration (nAMD) in both eyes for 2 years with recalcitrant choroidal neovascularisation (CNV) and had an episode of acute endophthalmitis in one eye was identified. After treatment of postinjection culture-negative right eye (RE) endophthalmitis with intravitreal vancomycin and tazobactam, the patient had complete regression of treatment-resistant CNV in RE to date with postinfection follow-up of 2 years. In contrast, the fellow eye continued showing activity in the choroidal neovascular membrane that required antivascular endothelial growth factor injections on a pro re nata basis to date. Prolonged regression of nAMD for 3 years in the affected eye and continued activity in the fellow eye support the hypothesis that inflammation accompanying endophthalmitis or the drugs used for the treatment can have a role in the regression of nAMD.

Purpose To describe two cases of catastrophic, bilateral retinal vascular occlusion following intravitreal (IVT) bevacizumab injection. Methods Case series. Main outcome measures included clinical and fluorescein angiography (FA) findings. Results Case 1 - A 65-year-old woman with calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasis (CREST) syndrome developed acute, severe, bilateral visual loss two weeks following bilateral IVT bevacizumab injection for proliferative diabetic retinopathy. Examination and FA revealed moderate anterior chamber inflammation, bilateral perivascular retinal hemorrhages and near total retinal vascular occlusion. Extensive testing revealed moderately elevated anti-B2 glycoprotein (antiphospholipid) antibodies. Case 2 - An 85-year-old man with polymyalgia rheumatica and left eye exudative age-related macular degeneration experienced severe, bilateral, sequential visual loss in the left then right eye approximately three weeks following IVT bevacizumab left eye injection. Examination revealed bilateral panuveitis, diffuse perivascular exudates, and intraretinal hemorrhages. FA showed diffuse venous leakage. Extensive testing revealed an elevated anti-nuclear antibody and mildly elevated anti-cardiolipin antibody. Conclusion Patients with underlying retinal vascular vulnerabilities may be at increased risk of catastrophic, bilateral retinal vascular occlusion following treatment with IVT bevacizumab. The moderate to severe intraocular inflammation in both cases, and the contralateral involvement following unilateral IVT injection in Case 2, suggest a possible delayed immune-mediated mechanism.

Purpose:To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD)., Methods:We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis., Results:In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001)., Conclusion:The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.

Cavitary optic disc anomalies can cause maculopathy. The most common of these associated with maculopathy is the optic disc pit. Very rarely, maculopathy can accompany optic disc coloboma. We report a case of combined cavitary disc anomalies (coloboma and disc pit) with maculopathy. A 22-year-old

To evaluate morphologic alterations in choroidal veins in eyes with typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).A retrospective review of baseline indocyanine green angiography in eyes with typical nAMD and PCV. We evaluated Haller layer veins in the early-phase indocyanine green angiography (before 2 minutes) for 1) macular anastomosis, 2) dilated Haller veins, and 3) focal variation in vessel caliber by at least 50% from the narrowest to largest diameters.We included 70 patients with gradable indocyanine green angiography for the prespecified features in the study eye (36 typical nAMD and 34 PCV) and 59 fellow eyes. The median subfoveal choroidal thickness was 167 µm versus 219 µm, P = 0.08, in the presenting eyes in typical nAMD and PCV, respectively. Macular anastomosis was common in both typical nAMD and PCV (presenting eyes 58.3% vs. 58.8%. P = 0.97; fellow eyes 65.5% vs. 63.3%, P = 0.86). Dilated Haller veins were numerically less common in typical nAMD than PCV (presenting eyes 52.8% vs. 67.6%, P = 0.21; fellow eyes 65.5% vs. 70.0%, P = 0.71), while vascular caliber variation was numerically more common in typical nAMD than PCV (presenting eyes 72.2% vs. 63.8%, P = 0.45; fellow eyes 69.0% vs. 56.7%, P = 0.33). The presence of all three features was more common in the presenting eyes with PCV compared with typical nAMD (35.3% vs. 13.9%, P = 0.03). In a multivariable analysis, every increase of 100 µm of CT conferred a 2.75 risk of having all three features present.Choroidal vascular remodeling is common in both tAMD and PCV but may be driven by different stimuli.

Purpose: To evaluate changes in cone functions using light-adapted (LA) 30 Hz flicker and LA 3.0 electroretinography (ERG) in intravitreal ranibizumab (IVR)-treated naïve neovascular age-related macular degeneration (nAMD) patients. Materials and methods: This retrospective interventional study reviewed the medical records of 32 nAMD patients (32 eyes) who received monthly IVR between January 2019 and January 2021. A comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA) testing and slit-lamp biomicroscopy, was performed as part of their clinical care, followed by LA 30 Hz flicker and LA 3.0 ERGs, optical coherence tomography, and fundus fluorescein angiography. All measurements were taken before IVR (baseline), as well as at months 6 and 12 later. Treatment was resumed for up to 12 months if recurrence occurred. Results: Compared to baseline, visual acuity improved significantly at months 6 and 12, respectively, coinciding with a significant decrease in central macular thickness (p < 0.05 for all). LA 30 Hz flicker ERG b-wave amplitude decreased significantly between baseline and months 6 and 12, respectively (p < 0.05 for both). There were no significant changes in LA 3.0 ERG a- and b-wave amplitudes between baseline and month 6 (p > 0.05 for both), but a significant decrease existed between baseline and month 12 (p < 0.05 for both). While LA 3.0 ERG a-wave implicit time increased significantly (p < 0.05 for both) between baseline and months 6 and 12, respectively, b-wave implicit time did not (p > 0.05 for both). Also, LA 30 Hz flicker ERG b-wave implicit times did not differ significantly between baseline and months 6 and 12, respectively (p > 0.05, for both). Conclusions: IVR was associated with long-term electrophysiological changes in cone functions, as measured by LA 30 Hz flicker and LA 3.0 ERGs. © 2022 Taylor & Francis Group, LLC.

To identify the risk factors associated with myopic macular neovascularization (mMNV)-related complications in patients treated with intravitreal anti-VEGF agents.Longitudinal cohort study.Myopic eyes (n = 313) with active mMNV and median (interquartile range) follow-up of 42 months (interquartile range, 18-68 months) after initiation of anti-VEGF treatment.Data regarding patients' clinical and mMNV-related characteristics were collected at baseline. Subsequent OCT scans were inspected for mMNV-related complications. Best-measured visual acuity (BMVA) values were retrieved from each visit.Incidence rate and hazard ratio (HR, with 95% confidence interval [CI]) of risk factors for fibrosis and macular atrophy calculated with Kaplan-Meier curves and Cox regression models. Crude incidence of macular hole (MH). Longitudinal BMVA changes.Five-year incidence of fibrosis, atrophy, and MH were 34%, 26%, and 8%, respectively. The rate of fibrosis was 10.3 (95% CI, 8.25-12.6) per 100 person-years. Risk factors were subfoveal mMNV location (HR [95% CI] = 12.7 [2.70-56.7] vs. extrafoveal, P = 0.001) and intraretinal fluid at baseline (HR [95% CI] = 1.75 [1.05-2.98], P = 0.03). The rate of macular atrophy was 6.5 (95% CI, 5-8.3) per 100 person-years. Risk factors were diffuse (HR, 2.20 vs. tessellated fundus; 95% CI, 1.13-5.45; P = 0.02) or patchy chorioretinal atrophy (HR, 3.17 vs. tessellated fundus; 95% CI, 1.32-7.64; P = 0.01) at baseline and more numerous anti-VEGF injections before baseline (HR, 1.21; 95% CI, 1.06-1.38 for each treatment; P = 0.005). Eyes with fibrosis and macular atrophy had faster BMVA decay over follow-up. Twenty eyes (6%) developed MH. Two subtypes of MH were identified: "atrophic" and "tractional."Myopic MNV-related complications are common in the long term despite initially successful treatment and have detrimental effects on visual acuity. Insights into their incidence and risk factors may help for future treatments to mitigate sight-threatening outcomes.

To investigate the suitability of 6 rod- or cone-mediated dark adaptation (DA) parameters as outcome measures for clinical trials in age-related macular degeneration (AMD), including their retest reliability, association with age and disease severity, and measurable longitudinal change over time.Prospective, longitudinal study (Clinicaltrials.gov: NCT01352975).A total of 191 patients with AMD and older participants followed longitudinally over 5 years.Dark adaptation testing was performed using the AdaptDx dark adaptometer with a maximum test time of 40 minutes. A 2-part exponential-linear curve was fitted to obtain values for cone decay, cone plateau, time to rod-cone break, rod intercept time (RIT), rod adaptation rate (S2), and area under the curve. Intersession retest reliability was assessed in tests performed within 2 weeks using the Bland-Altman analysis. The relationship of DA parameters with age, AMD severity, and reticular pseudodrusen (RPD) presence was evaluated using linear mixed models.Retest reliability, association with disease severity, and longitudinal change of 6 DA parameters.A total of 1329 DA curves were analyzed. Rod intercept time was the parameter that showed the greatest reliability (intraclass correlation coefficient of 0.88) and greatest association with age, AMD severity, and RPD (marginal RAge-related macular degeneration severity and RPD presence are each associated with large differences in multiple DA curve parameters. In addition, substantial differences in some parameters occur with age, even accounting for AMD severity and RPD status. This supports the 2-hit hypothesis of age and disease status on DA (and perhaps AMD pathophysiology itself). Of the DA parameters, RIT has the highest retest reliability, closest correlation with AMD severity and RPD, and largest longitudinal changes. This underscores the suitability of RIT as an outcome measure in clinical trials. The cone plateau increases only in advanced stages of kinetic rod dysfunction, indicating rod dysfunction preceding cone dysfunction and degeneration in the temporal sequence of pathology in AMD.

To determine prevalence of probable polypoidal choroidal vasculopathy (PCV) among White patients with neovascular age-related macular degeneration (nAMD) using non-indocyanine green angiography (ICGA) criteria DESIGN: Multicenter, multinational, retrospective, cross-sectional study.A total of 208 treatment-naive eyes from Hispanic and non-Hispanic White individuals diagnosed with nAMD were included. All underwent color fundus photography (CFP), optical coherence tomography (OCT), and fluorescein angiography (FFA). De-identified images of study eyes were sent to 2 groups of graders. Group 1 reviewed CFP, OCT, and FFA to confirm nAMD diagnosis. Group 2 reviewed CFP and OCT to determine highly suggestive features for PCV. Probable PCV diagnosis defined as the presence of ≥2 of 4 highly suggestive features for PCV: notched or fibrovascular pigment epithelial detachment (PED) on CFP, sharply-peaked PED, notched PED, and hyperreflective ring on OCT.Eleven eyes were excluded because of poor image quality (6) or non-nAMD diagnosis (5). Of 197 eligible eyes (197 patients), the mean age (SD) was 78.8 years (8.9), 44.2% were men, 26.4% were Hispanic, and 73.6% were non-Hispanic White individuals; 41.1%, 23.4%, 9.1%, and 2.5% had ≥1, ≥2, ≥3, and 4 highly suggestive features. Results showed that 23.4% (95% CI, 17.6%-29.9%) had probable PCV diagnosis. Predominantly occult CNV was more frequently found in probable PCV than nAMD subgroup (84.8% vs 64.9%, P = .01). Hispanic White individuals had a lower prevalence of probable PCV than non-Hispanic White individuals (9.6% vs 28.2%, P = .006) CONCLUSIONS: These findings suggest that probable PCV occurs between 17.6% and 29.9% in White individuals with nAMD, and more commonly in non-Hispanic than in Hispanic White individuals.

Neovascular age-related macular degeneration (nAMD) often requires intensive therapy with anti-VEGF injections. In prior post hoc studies, early residual fluid (ERF) after the loading phase was associated with poorer treatment outcomes. This retrospective study examined the impact of ERF on vision using machine learning (ML) methods in routine clinical practice.Retrospective cohort.This study included treatment-naïve patients with nAMD who were initiated on anti-VEGF between 2012 and 2018, with at least 1 year of follow-up.Overall, 286 patients with nAMD were included. An ML algorithm quantified intraretinal fluid (IRF), subretinal fluid (SRF), and total retinal fluid from OCTs. The ERF group included those with fluid at week 12 and was further stratified by fluid subtype. Paired t tests and analysis of variance compared best visual acuity (BVA) and fluid among subgroups, and a quartile analysis correlated fluid volumes to week 52 BVA. The risk of ERF was predicted from baseline factors using 3 ML methods: Ridge logistic regression, k nearest neighbors classification, and support vector classification.Mean change in BVA from baseline to week 52 according to week 12 fluid status.At week 12, 58.4% of patients had ERF. The breakdown of those in the ERF group included SRF-only (45.5%), IRF-only (21.6%), and IRF and SRF (32.9%). The ERF and ERF-free groups had similar BVA gains from baseline to week 52 (+5.7 ± 15.4 vs. +4.9 ± 18; P = 0.69). Examining specific ERF subgroups revealed no significant differences among the IRF-only (+4.6 ± 16.4), SRF-only (+5.6 ± 12.5), and IRF and SRF (+6.6 ± 18.5, P = 0.93) groups. Quartile analysis of week 12 fluid revealed no predictive pattern for BVA gains. Three ML methods were developed to predict those at risk for ERF achieved equivalent performance, with F1 score of 0.73 to 0.76.These results diverge from prior post hoc studies, in that there was no significant difference in long-term BVA gains between ERF and ERF-free cohorts, as well as between the week 12 fluid subgroups.

A 78-year-old man presented with moderate lens opacity and end-stage dry age-related macular degeneration (AMD) with visual acuity of logMAR 0.7 and 1.6 for right and left eyes, respectively. He was tested with an external telescope simulator device, showing an improvement of 20 letters and 2

Morning glory disc (MGD) is known to develop secondary maculopathy and vision loss. We followed a 7-year-old girl with MGD in right eye from 2010 to 2021. Her best-corrected Snellen visual acuity (BCVA) was 20/20 in both eyes till 2017. She presented with reduced vision in right eye with BCVA of 20/80 in 2018. Optical Coherence Tomography (OCT) revealed maculopathy related to MGD in right eye and arcuate Vitelliform neurosensory detachment (V-NSD) temporal to fovea. She underwent 25G vitrectomy with internal limiting membrane peeling. Resolution of retinoschisis and V-NSD was analysed by OCT and fundus autofluorescence (FAF) postoperatively. Arcuate V-NSD was hyperfluorescent on FAF and concentric to optic disc. It resolved slowly with BCVA improving to 20/20 at 18 and 30 months postoperatively. We report excellent outcome following early vitrectomy for MGD-related maculopathy and recommend serial follow-up and considering early vitrectomy whenever traction and BCVA worsens. We also describe arcuate V-NSD with MGD.

A 35-year-old woman presented with acute-onset painless diminution of vision for both distance and near in her left eye for 1 month. She is a known case of hypothyroidism controlled on oral thyroxine. The best-corrected visual acuity (BCVA) at presentation was 20/20 (spherical equivalent of −0.5 D

IMPORTANCE: The study team investigated costs associated with the ranibizumab port delivery system (PDS) for neovascular age-related macular (nAMD), an alternative to conventional intravitreal anti–vascular endothelial growth factor (VEGF) injections. OBJECTIVE: To investigate costs of intravitreal anti-VEGF injections vs ranibizumab PDS for patients with neovascular AMD (nAMD). DESIGN, SETTING, AND PARTICIPANTS: This cost analysis used trial data and Medicare reimbursement rates and included patients with nAMD who were receiving ranibizumab, aflibercept, bevacizumab injections, or ranibizumab PDS. MAIN OUTCOMES AND MEASURES: The number of intravitreal ranibizumab, aflibercept, and bevacizumab injections to break even with costs of ranibizumab PDS. Total direct medical costs over 1 year and 5 years for the ranibizumab PDS arm with refills at fixed 6-month intervals compared with monthly or bimonthly injections were calculated using Medicare rates. Scenario and sensitivity analyses accounted for uncertainty and variation. RESULTS: The mean (SD) number of ranibizumab, aflibercept, and bevacizumab injections to break even with the cost of ranibizumab PDS with 1 refill was 10.8 (1.3), 9.3 (1.1), and 34.5 (4.2), respectively. Ranibizumab PDS with fixed 6-month refills over 1 year cost $21 016 ($2102). Comparatively, monthly intravitreal ranibizumab cost $1943 (95% CI, −$3047 to $6932; P = .34) more, aflibercept cost $5702 (95% CI, $253-$11 151; P = .04) more, and bevacizumab cost $16 732 (95% CI, −$20 170 to −$13 294, P

BACKGROUND: Variants in RCBTB1 were recently described to cause a retinal dystrophy with only eight families described to date and a predominant phenotype of macular atrophy and peripheral reticular degeneration. Here, we further evaluate the genotypic and phenotypic characteristics of biallelic RCBTB1-associated retinal dystrophy in a North American clinic population. METHODS: A retrospective analysis of genetic and clinical features was performed in individuals with biallelic variants in RCBTB1. RESULTS: Three unrelated individuals of French-Canadian descent with rare biallelic RCBTB1 variants were identified. All individuals shared a novel p.(Ser342Leu) missense variant; one patient was homozygous whereas the other two each possessed a second unique novel variant p.(Gln120*) and p.(Pro224Leu). All three had macular-predominant disease with symptom onset in the fifth decade of life. CONCLUSION: This report adds to the genetic diversity of RCBTB1-associated disease. These cases confirm the later-onset, relative to many other retinal dystrophies, and macular focus of disease described in most cases to-date. They are thus a reminder of considering hereditary disease in the differential for later-onset macular atrophy.

Age-related macular degeneration (AMD) is a debilitating eye disease that tends to affect people over the age of 55. Lipofuscins are autofluorescent, toxic byproducts of the visual cycle thought to contribute toward the progression of the disease. Targeting the accumulation of lipofuscin through catabolism may serve as a method for the early treatment of AMD. Thus, an enzymatic approach capable of degrading lipofuscin, cycloretinal (all

A 31-year-old male with acute blurred vision and respiratory distress occurring three days after a penile filler injection was found to have outer plexiform layer hyperreflectivity on optical coherence tomography (OCT), consistent with paracentral acute middle maculopathy (PAMM). He was diagnosed with diffuse bilateral pneumonitis and silicone embolism syndrome requiring inpatient management. Following systemic stabilization, his vision and OCT findings improved. PAMM may be associated with silicone embolism syndrome in the presence of acute central scotomas and minimal retinal findings. Penile filler injections could contribute to retinal vaso-occlusion via an embolic process. PAMM may be self-limited and result in functional vision. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:635–638.]

To investigate the outcomes of macular buckling combined with vitrectomy and inverted internal limiting membrane flap technique for highly myopic full-thickness macular hole (FTMH) with macular retinoschisis.Twenty-six eyes of 26 consecutive patients were retrospectively included. Twelve eyes underwent macular buckling alone (buckling group). Fourteen eyes underwent macular buckling and vitrectomy with an inverted internal limiting membrane flap technique (combination group). Patients were followed for at least 9 months. Rates of FTMH closure and macular retinoschisis resolution, best-corrected visual acuity gained at the final visit were evaluated.The mean follow-up time was 13.00 ± 3.16 months. FTMH closed in six eyes (50%) of the buckling group and 13 eyes (92.86%) of the combination group ( P = 0.026) at the final visit. The macular retinoschisis resolution rate was close between two groups (100% vs. 92.86%; P = 1.000). Both groups achieved significant improvement in best-corrected visual acuity (10.42 ± 17.25 and 16.36 ± 10.39 Early Treatment Diabetic Retinopathy Study letters; P = 0.014 and P0.001). The combination group achieved slightly more best-corrected visual acuity improvement, but the difference fell short of significance ( P =0.312).Combination of macular buckling and vitrectomy with the inverted internal limiting membrane flap technique could achieve a high FTMH closure rate and significant best-corrected visual acuity improvement in FTMH with macular retinoschisis.

Myopic traction maculopathy (MTM), one of the complications of pathologic myopia, is a spectrum of pathological conditions that are attributed to tractional changes in the eye characterized by retinoschisis, lamellar or full thickness macular hole, and foveal retinal detachment. Considering the global public health burden of MTM and pathologic myopia, it is important to understand these sight-threatening complications and their associations. We conducted an evidence-based review of the prevalence and natural history of MTM and associated risk factors. The prevalence of MTM in the general population is low, but is increased among high myopes. MTM is associated with preretinal tractional structures, myopic refractive error and axial elongation, posterior staphyloma, dome-shaped macula, chorioretinal atrophy, and myopic macular degeneration. The clinical course of MTM tends to be stable; however, MTM may progress, resulting in visual acuity deterioration, although spontaneous improvement also occurs. The associations of MTM progression include vitreous traction, location, and extent of MTM, and lamellar macular hole-specific factors. More high-quality population-based studies that assess MTM prevalence and natural history are needed.

To examine the risk, prevalence, and progression of glaucoma development in age-related macular degeneration (AMD) eyes receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections compared to controls.Retrospective clinical cohort study.Retrospective review of eyes receiving intravitreal anti-VEGF injections from January 1, 2004, to December 31, 2013, for exudative AMD. Age- and sex-matched control groups of eyes included eyes with nonexudative AMD (NEAMD) and no AMD. Eyes with a diagnosis of glaucoma or glaucoma suspect were reviewed for injection details, type and date of glaucoma diagnosis, glaucoma treatments, standard automated perimetry (SAP), and spectral domain optical coherence tomography (SD-OCT). Qualitative progression was determined by indication of glaucoma progression in provider notes. Quantitative progression was assessed based on change in mean deviation (MD) on SAP, retinal nerve fiber layer thickness on SD-OCT, and intraocular pressure (IOP).There were 707 eyes of 504 patients treated with anti-VEGF injections and 1008 eyes in the NEAMD and no-AMD cohorts. There was no difference in glaucoma or suspect prevalence at initial presentation between eyes treated with injections and NEAMD (6.9% vs 9.7%, P = .22) or no-AMD controls (vs 8.5%, P = .55). There was no difference in cumulative 5-year probability of new glaucoma diagnosis after anti-VEGF injections compared to NEAMD (1.9% vs 1.0%, P = .69) or no-AMD controls (vs 1.6%, P = .88). There was no difference in qualitative progression of glaucoma in the injection cohort vs NEAMD (P = .19) or no-AMD controls (P = .61). The rate of MD change in injection eyes was similar to NEAMD eyes (P = .74) but greater than no-AMD eyes (P = .02). Eyes receiving injections required more topical glaucoma medications compared with NEAMD (P = .03) and more glaucoma laser treatments compared with no-AMD controls (P = .009). Eyes receiving injections did not require more frequent incisional glaucoma surgery compared with NEAMD (21.0% vs 15.0%, P = .95) or no-AMD controls (vs 10.0%, P = .10).Eyes treated with intravitreal anti-VEGF injections for exudative AMD did not have increased risk of developing glaucoma compared with controls. Of those with a glaucoma diagnosis, exudative AMD eyes receiving injections required a greater number of topical glaucoma medications compared with NEAMD eyes and had a greater rate of MD loss than no-AMD controls.

The concentrations of cytokines in plasma may be different between neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). We studied plasma levels of cytokines in patients with nAMD and PCV and compared them with control individuals.This was a prospective, clinic-based, case-control study of treatment-naive participants (n=49) with PCV (n=24), nAMD (n=11), and cataract controls (n=14). We sampled fresh venous blood and isolated plasma for analysis. Plasma concentrations of 34 angiogenic and inflammatory cytokines were determined by Luminex bead-based multiplex array.After adjusting for gender and age using multivariate logistic analysis, we found that the plasma concentrations of monocyte chemoattractant protein-1, vascular endothelial growth factor (VEGF)-A, and VEGF-D significantly higher in both nAMD and PCV patients than those in controls (all P0.05, times in nAMD: 3.5, 4.3, and 13.8, respectively, times in PCV: 4.1, 4.0, and 11.5, respectively). In contrast, the plasma concentration of platelet-derived growth factor-BB was significantly lower in nAMD and PCV patients than those in controls (all P0.05, times in nAMD: 1.6, times in PCV: 1.7). The plasma levels of leukemia inhibitory factor in nAMD group were significantly higher compared with PCV group (P0.0167).Multiple cytokines involved in systemic inflammation and angiogenesis including monocyte chemoattractant protein-1, platelet-derived growth factor-BB, VEGF-A, and VEGF-D may contribute to the pathogenesis of nAMD and PCV. Measurement of leukemia inhibitory factor in the plasma may help differentiate nAMD from PCV. This finding suggests that the 2 disorders may have different molecular mechanisms, and additional longitudinal studies will be needed to determine whether these findings have clinical relevance to influence treatment algorithms or provide novel targets for medical therapy.

This meta-analysis investigates the incidence of intraocular inflammation (IOI) after intravitreal antivascular endothelial growth factor injections in neovascular age-related macular degeneration.A systematic search was performed on Ovid MEDLINE, Embase, and Cochrane Central from January 2005 to April 2021. Randomized controlled trials comparing IOI after intravitreal bevacizumab, ranibizumab, brolucizumab, or aflibercept in neovascular age-related macular degeneration were included. Primary outcomes were sight-threatening IOI, final best-corrected visual acuity, and change in best-corrected visual acuity from baseline. Secondary outcomes included the incidence of other IOI events. Meta-analysis was performed using a random-effects model.Overall, 11,460 unique studies were screened, of which 14 randomized controlled trials and 6,759 eyes at baseline were included. There was no difference between agents for the risk of endophthalmitis and retinal vascular occlusion. Compared with aflibercept, brolucizumab had a higher incidence of generalized IOI (risk ratio = 6.24, 95% confidence interval = [1.40-27.90]) and vitreous haze/floaters (risk ratio = 1.64, 95% confidence interval = [1.00-2.67]). There were no significant differences between comparators for other secondary end points.There was no difference in the risk of severe sight-threatening IOI outcomes between intravitreal antivascular endothelial growth factor agents. There was a significantly higher risk of generalized IOI after brolucizumab relative to aflibercept. Our results alongside other recent safety findings suggest the need for further investigation in the risk-benefit profile of brolucizumab for the treatment of neovascular age-related macular degeneration.

Charles Bonnet syndrome (CBS) is a disorder of visual hallucinations in psychologically normal patients with ocular disease or damage to visual pathways. The etiology of CBS is not fully understood. It is associated with various triggers, with age-related macular degeneration the most common; other triggers are systemic diseases such as stroke, multiple sclerosis, and anemia as well as lighting issues, fatigue, and medical or surgical eye treatments. Visual disturbances such as decreased visual acuity, visual field deficits, or visual hallucinations are common in association with hypertensive encephalopathy. We describe a patient with episodic CBS triggered by recurrent hypertensive crises, which resolved with blood pressure management in the hospital setting.

Age-related macular degeneration is a metabolic compromise disorder whose main pathological feature is choroidal neovascularization (CNV) formation. Using untargeted metabolomics analysis, we determined to assess the metabolomic alterations in a CNV rat model to provide an insight into its pathogenesis. In the CNV model, there were 24 significantly changed metabolites in the plasma and 71 in various ocular tissues. Pathway analysis showed that certain metabolic pathways changed in interrelated tissues: for instance, in terms of the altered urea cycle, arginine and proline metabolism were increased in the plasma, while spermidine and spermine biosynthesis activities were increased in the retinal pigment epithelium (RPE)/choroid. The retina and RPE/choroid shared the same changed metabolites of branched-chain amino acid metabolism. Fatty acid metabolism was found to be the significant altered metabolic pathway in the retina of this CNV model. Although the metabolism pattern of different substances is specific for each ocular tissue, there is also a certain material exchange between different tissues. Dysregulated metabolomic profiles in differential tissues may point to an interconnected pathway, oxidative stress response, which may lead to RPE cell degeneration and, ultimately, CNV development.

Objectives: To determine the prevalence of polypoidal choroidal vasculopathy (PCV) in intravitreal (IV) anti-vascular endothelial growth factor (anti-VEGF)-resistant neovascular age-related macular degeneration (nvAMD) cases. Materials and Methods: Eyes that were diagnosed as having active and treatment-naive nvAMD in the Ege University Ophthalmology Department, Retina Unit in 2011-2018, were non-responsive to IV anti-VEGF treatment, and for which indocyanine angiography (ICGA) could be obtained were included in the study. Active nvAMD was defined as the presence of fresh hemorrhage on clinical examination or findings of subretinal, intraretinal, or sub-retinal pigment epithelial fluid on spectral domain optical coherence tomography and accompanying fluorescein dye leakage in fluorescein angiography. Eyes that had activation findings despite at least 6 consecutive intravitreal anti-VEGF injections were defined as non-responders and underwent ICGA to assess for PCV. The diagnosis of PCV was based on the Everest II study criterion. Results: A total of 97 eyes of 88 patients were included in the study. Of 88 patients, 44 (50%) were female, 44 (50%) were male, and the mean age was 75.9±8.3 years (range: 59-93). The mean number of anti-VEGF injections until the time of ICGA was 7.3±2.2 (range: 6-15). PCV was detected in 62 eyes (63.9%) on ICGA. Conclusion: The prevalence of PCV is quite high among eyes with IV anti-VEGF treatment-resistant nvAMD in Turkey (63.9%). ICGA evaluation for PCV should be conducted for all nvAMD cases that are non-responsive to IV anti-VEGF treatment, both to shed light on the reason for resistance and to modify treatment as necessary. © 2022 by Turkish Ophthalmological Association Turkish Journal of Ophthalmology, published by Galenos Publishing House.

Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of melanin, we designed a therapeutic strategy for replenishment of melanin using PEGylated synthetic melanin-like nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are biocompatible and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for at least 3 months after a single-dose intravitreal injection. Our findings demonstrate that MNPs are able to substitute for natural melanin in the RPE and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD.

BACKGROUND AND OBJECTIVE: Macular atrophy (MA) contributes to declining vision during prolonged anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (nAMD) so greater understanding of its incidence, evolution, and impact on visual acuity is merited. MATERIALS AND METHODS: This is a retrospective review of nAMD patients receiving anti-VEGF therapy for ≥ 5 years. Near-infrared reflectance images and vision data were extracted every 6 months. MA lesion areas were measured using ImageJ. RESULTS: Vision showed a mean decline of −1.2 letters/year. Eyes with MA showed a greater decrease of −1.6 letters/year compared to eyes without MA (−0.7 letters/year). Cumulative incidence of MA was 38% at 5 years. MA was significantly associated with declining vision, showing a −0.7 letter decrease for every 1 mm 2 increase in lesion size. CONCLUSION: Over a 5-year course of nAMD treatment, MA affected most eyes, and MA progression was significantly associated with vision decline. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:546–552.]

Vascular endothelial growth factor（VEGF）, fibroblast growth factor（FGF）, nerve growth factor（NGF）, epidermal growth factor and interferon are important endogenous proteins that regulate cell proliferation, differentiation and regeneration. Biological products targeting growth factors are used in the treatment of ocular diseases such as wet age-related macular degeneration, corneal injury and neurotrophic keratitis. Anti-VEGF drugs can regulate the proliferation of vascular endothelia, reduce the edema and exudation of retinal tissue，which are the main therapeutic agents for wet age-related macular degeneration and diabetic retinopathy. The basic FGF (b-FGF) can promote the proliferation, differentiation, and migration of corneal epithelial cells, accelerating the healing of the corneal injury and reduces corneal inflammation；and bovine b-FGF has been approved for the treatment of corneal injuries. The NGF promotes the growth, development, and differentiation of central and peripheral neurons, thus accelerating the repair of nerve damage；and the European Medicines Agency approved the use of nerve growth factor for the treatment of neurotrophic keratitis in 2017. Recent clinical studies show that patients with moderate or severe neurotrophic keratitis achieved complete corneal healing following 8 weeks of NGF therapy. Epidermal growth factor derivative eye drops have been approved for the treatment of corneal epithelial injuries. Recombinant human interferon has been clinically used in the treatment of ocular viral infections. This article reviews the research progress in the development of new cell growth factor drugs for the treatment of ophthalmic diseases, to provide insights for expanding the application of cell growth factors in ophthalmology.

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. Oxidative stress-induced retinal pigment epithelium (RPE) cell apoptosis is a crucial pathogenic hallmark in AMD. Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a prostaglandin (PG) D2 receptor, has been implicated in various pathophysiological events, especially inflammation and stress-induced cell apoptosis. However, its specific role in AMD is not fully understood. Here we studied the effect of CRTH2 on AMD. Our results showed that when stimulated by H

The RENOWNED study investigated the treatment patterns, real-world effectiveness and safety of ranibizumab in Taiwanese patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg in accordance with the first reimbursement scheme effective from 2012 to 2014.This study was a Phase IV, 12-month, open-label, prospective, observational study conducted in Taiwan. Patients with visual impairment due to nAMD initiating treatment with ranibizumab 0.5 mg were included. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from Baseline at Month 3.Overall, 202 patients with nAMD were included. Mean (standard deviation [SD]) BCVA Early Treatment Diabetic Retinopathy Study letters improved from Baseline (49.6 [21.5] letters) at Month 3 (+4.9 [11.8], P 0.0001), and at Month 12 (+3.5 [14.1], P = 0.0043). The proportion of patients with nAMD who lost ≥5 letters at Months 3 and 12 was 13.6% (n = 27) and 26.6% (n = 37), respectively. Mean (SD) central retinal thickness decreased from Baseline (320.1 [127.2] μm) with a mean reduction of 49.1 (107.3) μm at Month 3 (P 0.0001), but was not significant at Month 12 with a mean reduction of 11.6 (115.6) μm (P = 0.2861). Mean (SD) number of ranibizumab injections over 12 months was 3.1 (1.0). A mean treatment interval of 109.5 days was observed between the third and fourth injections. After limited reimbursed ranibizumab injections, 43.8% patients received other treatments. The safety findings are consistent with previous studies.Ranibizumab 0.5 mg treatment for 12 months under real-world settings improved visual outcomes in Taiwanese patients with nAMD.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the gold standard treatment for wet age-related macular degeneration (wet AMD). Coronavirus disease 2019 (COVID-19) has led to the cancellation of many scheduled intravitreal anti-VEGF injection visits. We compared the functional and structural visual outcomes of wet AMD patients who did not adhere to their planned intervals (group 1) with those who did (group 2).Wet AMD patients of Swiss Visio Montchoisi and RétinElysée were included. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) changes between their first visit after the end of the first national lockdown in Switzerland (27 April 2020, first post-lockdown visit) and their last visit before the beginning of the first national lockdown in Switzerland (13 March 2020, last pre-lockdown visit) were assessed. The BCVA outcome was defined as unfavorable when there was a loss of≥5 ETDRS letters in the first post-lockdown visit compared to the BCVA at last pre-lockdown visit. The OCT outcome was defined as unfavorable when there was an increase in at least one of the parameters, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment (PED), at the first post-lockdown visit compared to the last pre-lockdown visit.Group 1 (89 patients, 109 eyes) had a 13.41% greater rate of unfavorable BCVA outcomes and a 38.27% greater rate of unfavorable OCT outcomes than group 2 (96 patients, 122 eyes) (P=0.04, P0.0001, respectively). Multivariate analysis showed that the more the patients deviated from their programmed injections and the higher the BCVA pre-lockdown, the higher the rate of unfavorable BCVA outcomes (P=0.03 and P=0.02, respectively). OCT outcomes were not a predictive factor for an unfavorable BCVA outcome.The cancellation of many intravitreal anti-VEGF injection appointments resulted in worse functional and structural outcomes in wet AMD patients. The COVID-19 pandemic led many patients to refrain from their routine intravitreal anti-VEGF injection appointments, allowing us to analyze the role of designated intervals in the treatment of wet AMD. During any future lockdown due to COVID-19 or similar circumstances, continuity of care for wet AMD patients should be maintained.

To compare the enlargement rates of geographic atrophy (GA) over 5 years of follow-up with those of macular atrophy (MA) associated with macular neovascularization (MNV).Retrospective, longitudinal, comparative case series.Consecutive series of patients with age-related macular degeneration and GA (dry) or with MA and MNV.Atrophic regions detected on serial registered fundus autofluorescence images were semiautomatically delineated, and the measurements of these areas were recorded every 6 ± 3 months for the first 2 years of follow-up and at yearly intervals for up to 5 years.Annual raw and square root-transformed rates of atrophy growth.The study included 117 eyes of 95 patients (61 in the GA cohort and 56 in the MA cohort); 100% and 38.5% of the eyes completed 2 and 5 years of follow-up, respectively. The mean size of lesions at baseline was similar between the 2 groups (raw: 1.74 vs. 1.53 mmThe presence of MNV was associated with a slower rate of expansion, resulting in overall smaller areas of atrophy over time. These findings support the hypothesis that MNV may protect against the progression of atrophy.

To assess the association between treatment interval and likelihood of anti-vascular endothelial growth factor (anti-VEGF) discontinuation among patients with neovascular age-related macular degeneration (nAMD) in a real-world setting in the United States.Retrospective clinical cohort study.Health insurance claims data from the IBM MarketScan Commercial and Medicare Supplemental databases were retrospectively reviewed to identify adults with nAMD who received anti-VEGF for the first time between July 1, 2011, and June 30, 2017. The proportion of discontinued patients was analyzed using Kaplan-Meier curves. Cox proportional hazards models were used to examine the association between treatment intervals at 24 months and anti-VEGF discontinuation.The analysis included 8167 patients on continuous, unilateral anti-VEGF treatment for at least 24 months. Baseline demographics and clinical characteristics were well balanced between treatment interval groups. The overall rate of discontinuation from 24 months until 60 months after treatment initiation was 30.4%. At 60 months, patients on shorter treatment intervals were more likely to remain on treatment than those on longer intervals, ranging from 76.8% (4-week interval group) to 60.6% (12-week interval group) and corresponding to a 28% lower likelihood (HR [SE] 0.72 [0.12], P.01) and 55% higher likelihood of discontinuing treatment (HR [SE] 1.55 [0.07], P.01), respectively, compared with the 8-week group.nAMD patients on longer anti-VEGF treatment intervals at 24 months had consistently higher discontinuation rates than patients on shorter intervals in the following years. This highlights the need to support and educate patients on long treatment intervals to continue with their treatment.

To evaluate the outcomes of a 6-month follow-up after switching to brolucizumab from aflibercept to treat neovascular age-related macular degeneration (AMD) in Japanese patients.Retrospective observational study.We studied 45 consecutive eyes of 42 patients diagnosed with neovascular AMD, who were switched to intravitreal brolucizumab injection (IVBr) after receiving intravitreal aflibercept injection (IVA) using a treat-and-extend (TAE) regimen. Patients who had brolucizumab-associated intraocular inflammation (IOI) were excluded from the study. The mean changes in the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), central foveal thickness (CFT), central choroidal thickness (CCT), and treatment intervals were evaluated at 6 months after the switch to IVBr.One eye of 1 patient was excluded because of IOI after the switch; 44 eyes of 41 patients were enrolled in this study. The mean logMAR BCVA was maintained throughout the follow-up period when compared with the baseline value (P .05 at 6 months). However, the mean CFT and CCT at 6 months had decreased significantly (P .05 and P .001, respectively). The mean treatment interval was extended from 5.75 to 8.12 weeks.Switching to brolucizumab from aflibercept using a TAE regimen might be effective for maintaining functional outcomes and extending intervals in Japanese patients with AMD.

The choriocapillaris, a dense capillary network located at the posterior pole of the eye, is essential for supporting normal vision, supplying nutrients, and removing waste products from photoreceptor cells and the retinal pigment epithelium. The anatomical location, heterogeneity, and homeostatic interactions with surrounding cell types make the choroid complex to study both in vivo and in vitro. Recent advances in single-cell RNA sequencing, in vivo imaging, and in vitro cell modeling are vastly improving our knowledge of the choroid and its role in normal health and in age-related macular degeneration (AMD). Histologically, loss of endothelial cells (ECs) of the choriocapillaris occurs early in AMD concomitant with elevated formation of the membrane attack complex of complement. Advanced imaging has allowed us to visualize early choroidal blood flow changes in AMD in living patients, supporting histological findings of loss of choroidal ECs. Single-cell RNA sequencing is being used to characterize choroidal cell types transcriptionally and discover their altered patterns of gene expression in aging and disease. Advances in induced pluripotent stem cell protocols and 3D cultures will allow us to closely mimic the in vivo microenvironment of the choroid in vitro to better understand the mechanism leading to choriocapillaris loss in AMD.

The retinal pigment epithelium (RPE) plays a crucial part in sight-threatening diseases. In this review, we shed light on the pivotal implication of the RPE in age-related macular degeneration, diabetic retinopathy and retinopathy of prematurity; and explain why a paradigm shift toward targeted RPE therapy is needed to efficiently fight these retinal diseases. We provide guidance for the development of RPE-specific nanotherapeutics by giving a comprehensive overview of the possibilities and challenges of drug delivery to the RPE and highlight successful nanotherapeutic approaches targeting the RPE.

Fluid in neovascular age-related macular degeneration is often used to assess patient response to anti-vascular endothelial growth factor therapy. Various studies theorize that early residual fluid (ERF), noted as persistence of intraretinal fluid and subretinal fluid after the anti-vascular endothelial growth factor loading phase (LP), may be predictive of visual outcomes. This meta-analysis examined the existing literature on the relationship between ERF and long-term visual acuity (VA) and found that those who were fluid-free after the LP tended to have the highest VA gains overall. Early intraretinal fluid appeared to be associated with reduced VA gains, whereas the impact of early sub-retinal fluid was more debated. For those with ERF, monthly or more frequent dosing regimens following the LP appeared most optimal for VA. As most studies in this review were post hoc analyses, this highlights the need for real-world studies investigating ERF and its effect on visual outcomes in neovascular age-related macular degeneration. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:506–513.]

To determine whether the rates of macular atrophy (MA) differ between eyes with neovascular age-related macular degeneration (nAMD) treated continuously with the Port Delivery System with ranibizumab (PDS) and those treated with ranibizumab given as a bolus intravitreal injection.A preplanned exploratory analysis of a phase 2, multicenter, randomized, active treatment-controlled, dose-ranging study.Patients diagnosed with nAMD within 9 months of screening who had received at least 2 previous intravitreal anti-vascular endothelial growth factor injections of any agent and were responsive to the treatment.Eyes were randomized (3:3:3:2) to treatment with either the PDS (filled with a customized formulation of ranibizumab at 10, 40, or 100 mg/ml and refilled pro re nata) or monthly intravitreal ranibizumab 0.5-mg injections.The prevalence, incidence, and progression of MA.The analysis population consisted of 220 eyes (58, 62, 59, and 41 eyes in the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg injection arms, respectively). At study baseline, MA was observed in 14.5% (PDS 10-mg/ml), 11.5% (PDS 40-mg/ml), 13.6% (PDS 100-mg/ml), and 7.6% (monthly ranibizumab) of eyes. At the last assessment (mean, 22.1 months), the prevalence of MA had increased to 38.6% (PDS 10-mg/ml), 40.0% (PDS 40-mg/ml), 40.4% (PDS 100-mg/ml), and 45.7% (monthly ranibizumab). In patients without MA at baseline, a higher proportion of eyes in the monthly ranibizumab arm (40.6%) developed MA than in those in the PDS arms (28.6%, 32.1%, and 30.6% of eyes in the PDS 10-, 40-, and 100-mg/ml arms, respectively). The mean change in the area of MA from baseline to the last assessment for the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly ranibizumab arms was +2.46, +1.61, +1.09, and +1.15 mmIn the phase 2 Ladder trial, there was no evidence of worse MA with the PDS compared with that with monthly intravitreal ranibizumab 0.5-mg injections. Larger trials focusing on MA are needed to confirm this finding.

To report a case of nonarteritic anterior ischemic optic neuropathy (NAION) after intravitreal injection in a patient with a history of fellow-eye NAION.Observational case report.An 82-year-old woman with a history of fellow eye NAION developed an inferior visual field defect 1 day after an intravitreal aflibercept injection for neovascular age-related macular degeneration. She was found to have optic disk edema and an inferior altitudinal defect, consistent with NAION. The mechanism may have involved compromised perfusion to the optic nerve head related to elevated intraocular pressure or vasoconstriction because of antivascular endothelial growth factor activity.Nonarteritic anterior ischemic optic neuropathy is a rare complication of intravitreal injection and may be related to postinjection elevation in intraocular pressure. Monitoring of intraocular pressure postinjection with low-threshold for preinjection aqueous suppression or postinjection anterior chamber paracentesis for persistently elevated intraocular pressure is recommended in patients with a history of NAION.

BACKGROUND. —: A major cause of blindness in older persons is age-related macular degeneration (AMD). Cigarette smoking is one of the major risk factors for AMD. In the present study, we analyzed UK Biobank data to determine whether smoking cannabis, like cigarettes, might be related to AMD. METHODS. —: Our UK Biobank application was approved as UKB project 57245 (S.L., P.H.R.). Our analysis included all subjects with AMD and cannabis smoking information. The diagnosis of AMD was ascertained based on the 10th Revision of the International Classification of Diseases (ICD10), H35.3. Age at time of diagnosis of AMD was obtained from data field 5923. Cannabis information was recorded in UKB category 143, data field 20453, ever taken cannabis. A touch screen posed the question, “Have you taken CANNABIS (cannabis, grass, hash, ganja, blow, draw, skunk, weed, spliff, dope), even if it was a long time ago?” Possible answers were no, yes, 1–2 times, yes 3–10 times, yes, 11–100 times, yes, more than 100 times. RESULTS. —: Subjects who had used marijuana more than 100 times had a significantly reduced risk of AMD, compared to subjects who had never used marijuana, and use of marijuana every day was associated with less AMD than use of marijuana less than once a month. But subjects who used cannabis 100 times or more were significantly younger (8 years) when they developed AMD than subjects who never used cannabis. CONCLUSION. —: Drusen, deposits of lipids, proteins, and cellular debris, accumulate in Bruch’s membrane, limiting transport between the retinal pigment epithelium and the vasculature, triggering an inflammatory reaction. Marijuana can retard the inflammatory process because it is a powerful anti-inflammatory agent. Therefore, marijuana could reduce the risk of AMD. At the same time, blood vessels in the choriocapillaris below Bruch’s membrane become more sparse with age. This phenomenon is believed to be a starting point for AMD. Marijuana can accelerate the loss of blood vessels due to its anti-angiogenic properties. Therefore, marijuana use might cause AMD to develop sooner in younger people.

We report the case of a 27-year-old monocular woman with a history of sickle cell disease who received intra-arterial tissue plasminogen activator (tPA) after presenting with acute painless vision loss secondary to incomplete central retinal artery occlusion presenting as paracentral acute middle maculopathy in her left eye.Ultrawidefield fundus photography, ultrawidefield fluorescein angiography, en face optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were obtained and reviewed, followed by cerebral angiography and infusion of intra-arterial tissue plasminogen activator.A patient with a history of sickle cell disease presented with a new onset of a dense central scotoma, and the visual acuity diminished to 20 of 200 from baseline 20 of 20 in her left eye. Fluorescein angiogram was nondiagnostic. Optical coherence tomography revealed perifoveal hyper-reflective bands in the inner nuclear layer in a pattern characteristic of paracentral acute middle maculopathy. The patient received intra-arterial tissue plasminogen activator through her left ophthalmic artery shortly after presentation, resulting in a gradual restoration of the visual acuity to 20 of 20 in the three months after the procedure.This is the first report describing the use of intra-arterial tissue plasminogen activator to treat incomplete central retinal artery occlusion presenting as a paracentral acute middle maculopathy lesion in a patient with sickle cell disease.

To apply an automated deep learning automated fluid algorithm on data from real-world management of patients with neovascular age-related macular degeneration for quantification of intraretinal/subretinal fluid volumes in optical coherence tomography images.Data from the Vienna Imaging Biomarker Eye Study (VIBES, 2007-2018) were analyzed. Databases were filtered for treatment-naive neovascular age-related macular degeneration with a baseline optical coherence tomography and at least one follow-up and 1,127 eyes included. Visual acuity and optical coherence tomography at baseline, Months 1 to 3/Years 1 to 5, age, sex, and treatment number were included. Artificial intelligence and certified manual grading were compared in a subanalysis of 20%. Main outcome measures were fluid volumes.Intraretinal/subretinal fluid volumes were maximum at baseline (intraretinal fluid: 21.5/76.6/107.1 nL; subretinal fluid 13.7/86/262.5 nL in the 1/3/6-mm area). Intraretinal fluid decreased to 5 nL at M1-M3 (1-mm) and increased to 11 nL (Y1) and 16 nL (Y5). Subretinal fluid decreased to a mean of 4 nL at M1-M3 (1-mm) and remained stable below 7 nL until Y5. Intraretinal fluid was the only variable that reflected VA change over time. Comparison with human expert readings confirmed an area under the curve of0.9.The Vienna Fluid Monitor can precisely quantify fluid volumes in optical coherence tomography images from clinical routine over 5 years. Automated tools will introduce precision medicine based on fluid guidance into real-world management of exudative disease, improving clinical outcomes while saving resources.

Age-related macular degeneration, a prevalent degenerative retinal disease, is associated with non-visual and psychosocial impairments that may affect sleep. In this systematic review, we evaluated associations between age-related macular degeneration (AMD) and sleep, highlighted knowledge gaps and provided evidence-based recommendations to clinicians to enable holistic management of AMD patients.We searched PubMed, Embase and the Cochrane Central registries for papers published before May 2022. Non-English, qualitative studies and grey literature were excluded. Studies evaluating the association between AMD and sleep (including sleep disorders like insomnia and sleep apnea), and vice versa, were included. The quality of shortlisted studies was evaluated using the Newcastle Ottawa Scale.Six (two case-control studies, three longitudinal cohort studies and one cross-sectional study) of 551 studies were included in this review. Four studies found that AMD was associated with increased rates of sleep apnea and poorer reported sleep quality, while five studies showed that patients with sleep apnea or insomnia were at higher risk of developing AMD. Associations between self-reported sleep quantity and AMD were conflicting. No study evaluated the relationship between AMD and sleep using objective sleep assessment tools.Only a limited number of studies investigated associations between AMD and sleep. These studies suggest a bidirectional relationship between AMD and sleep dysfunction yet disagree on the relationship between sleep quantity and the likelihood of AMD. Additional studies, using objective characterisation of sleep in patients with AMD are required to confirm these findings.

Observational studies have reported inconsistent results on the relationship between age-related macular degeneration (AMD) and Alzheimer's disease (AD). Therefore, we aimed to determine whether there is a causal association between AMD and AD.This two-sample bidirectional Mendelian randomization (MR) study evaluated causal associations between advanced AMD and AD using summary data from large genome-wide association studies.Genetic liability for advanced AMD showed no statistical causal association with AD risk (odds ratio [OR] = 0.999, 95% confidence interval [CI]: 0.955-1.044, P = .948). Reverse MR analysis provided little support for a causal effect of AD on advanced AMD (OR = 0.973, 95%CI: 0.938-1.008, P = .133).This MR study found no evidence to support a bidirectional causality between advanced AMD and AD.We evaluated the bidirectional causal relationship between advanced AMD and AD. Advanced AMD showed no statistical causal association with risk of AD. We found no evidence to support a causal effect of AD on advanced AMD risk. The associations observed in epidemiological studies should not be considered causal.

To identify patient preference drivers related to the management of wet age-related macular degeneration (wet AMD).In this cross-sectional study, a self-explicated 'conjoint analysis' survey was administered online to eligible patients with wet AMD (receiving anti-vascular endothelial growth factor [VEGF] treatment for at least 12 months) from the USA, Canada, UK, France, Spain, Germany, Italy, Japan, Taiwan, and Australia. The survey consisted of six domains with 21 attributes, which were selected on the basis of a literature review, social media listening, and tele-interviews/discussions with patients, clinical experts, and patient groups. Utility and relative importance scores were generated for each attribute and utility difference significance testing was performed using 'unequal variances t tests'. The Patient Activation Measure (PAM-13) questionnaire was administered to assess patients' knowledge, skill, and confidence in self-management.A total of 466 patients (mean age, 68 years; women, 54%; binocular wet AMD, 28%) with an average anti-VEGF treatment duration of 3.9 years completed the survey. The most important preference domains were 'treatment effects on vision' (non-significant) and 'vision-related symptom burdens' (p 0.001), followed by 'treatment risk' (p 0.05), 'impact on daily activities' (p 0.05), 'burden of clinic/hospital visits' (p 0.001), and 'impact on psychological well-being'. The five most important attributes in order of importance were clarity of vision, treatment effect on symptoms, quality of vision, time to treatment effect, and time to re-administration. The two most important attributes globally were also in the top three attributes across countries. The majority of participants in the study were level 3 or level 4 of the PAM-13 questionnaire.This study identified the most important disease and treatment attributes to patients using patient-centred methods. The data showed the degree of harmonization of preferences across geographies and that participants actively adopt behaviours required for improved treatment outcomes. The identified preference drivers may inform future clinical development.