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Glaucoma is the leading cause of blindness throughout the world (after cataracts); therefore, general physicians should be familiar with the diagnosis and management of affected patients. Glaucomas are usually categorized by the anatomy of the anterior chamber angle (open vs narrow/closed), rapidity of onset (acute vs chronic), and major etiology (primary vs secondary). Most glaucomas are primary (ie, without a contributing comorbidity); however, several coexisting ophthalmic conditions may serve as the underlying etiologies of secondary glaucomas. Chronic glaucoma occurs most commonly; thus, regular eye examinations should be performed in at-risk patients to prevent the insidious loss of vision that can develop before diagnosis. Glaucoma damages the optic nerve and retinal nerve fiber layer, leading to peripheral and central visual field defects. Elevated intraocular pressure (IOP), a crucial determinant of disease progression, remains the only modifiable risk factor; thus, all current treatments (medications, lasers, and operations) aim to reduce the IOP. Pharmacotherapy is the usual first-line therapy, but noncompliance, undesirable adverse effects, and cost limit effectiveness. Laser and surgical treatments may lower IOP significantly over long periods and may be more cost effective than pharmacotherapy, but they are plagued by greater procedural risks and frequent treatment failures. Traditional incisional procedures have recently been replaced by several novel, minimally invasive glaucoma surgeries with improved safety profiles and only minimal decreases in efficacy. Minimally invasive glaucoma surgeries have dramatically transformed the surgical management of glaucoma; nevertheless, large, randomized trials are required to assess their long-term efficacy.

Macular telangiectasia Type 2 (MacTel) is a gradually progressive disease that affects the quality of life by impairing both distant and near vision. It had previously been considered a vascular condition, but recent evidence suggests a neurodegenerative etiology, with primary involvement of Muller cells. Retinal pigment epithelium (RPE) hyperplasia and subretinal neovascularization (SNV) are responsible for most of the vision loss in advanced cases. Neurotrophic factors in the non-proliferative phase and intravitreal anti-Vascular Endothelial growth factor (VEGF) in the proliferative phase have shown to retard the progression of the disease. This review will discuss the pathophysiology, clinical features, important diagnostic imaging studies and available treatment options for MacTel.

To evaluate the safety and therapeutic effects of orally administered AKST4290 (formerly BI 144807 and ALK4290) in treatment-naive patients with neovascular age-related macular degeneration.In this prospective, multicenter, open-label Phase 2a pilot clinical study, 30 patients with newly diagnosed neovascular age-related macular degeneration self-administered AKST4290 (400 mg) orally twice daily for 6 weeks. Patients were examined weekly for safety, to measure best-corrected visual acuity (BCVA), and to perform exploratory morphologic assessments. The primary endpoint was the mean change in BCVA from baseline to end of treatment, and the secondary endpoint was safety. Exploratory endpoints investigated potential changes in macular morphology.Mean BCVA improved by +7.0 letters (95% CI, 2.2-11.7); 24 patients (82.8%) had stable or improved BCVA, with 6 (20.7%) gaining ≥15 letters. No patients experienced severe or serious adverse events.In this 6-week study, AKST4290 treatment was associated with improved BCVA scores in patients with treatment-naive neovascular age-related macular degeneration. All adverse events were mild or moderate in severity and no safety issues were identified. Treatment of neovascular age-related macular degeneration with AKST4290 warrants further investigation in randomized, placebo-controlled trials.

Understanding the impact of fluid in different retinal compartments is critical to developing treatment paradigms that optimize visual acuity and reduce treatment burden in neovascular age-related macular degeneration. This systematic review aimed to determine the impact of persistent/new subretinal fluid, intraretinal fluid, and subretinal pigment epithelial fluid on visual acuity over 1 year of treatment.Publication eligibility and data extraction were conducted according to Cochrane methods: 27 of the 1,797 screened records were eligible.Intraretinal fluid negatively affected visual acuity at baseline and throughout treatment, with foveal intraretinal fluid associated with lower visual acuity than extrafoveal intraretinal fluid. Some studies found that subretinal fluid (particularly subfoveal) was associated with higher visual acuity at Year 1 and longer term, and others suggested subretinal fluid did not affect visual acuity at Years 1 and 2. Data on the effects of subretinal pigment epithelial fluid were scarce, and consensus was not reached. Few studies reported numbers of injections associated with fluid status.To optimally manage neovascular age-related macular degeneration, clinicians should understand the impact of fluid compartments on visual acuity. After initial treatment, antivascular endothelial growth factor regimens that tolerate stable subretinal fluid (if visual acuity is stable/improved) but not intraretinal fluid may enable patients to achieve their best possible visual acuity. Confirmatory studies are required to validate these findings.

Introduction To assess the safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab® (Intas Pharmaceuticals, Ahmedabad, India) in chorioretinal disorders under real-world conditions. Methods This was a multicenter, retrospective chart review which included patients from 15 centers receiving intravitreal Razumab (IVRz) injections from 2016 to 2020. Patient demographics, ocular examination data, and detailed safety information regarding serious adverse events (SAE) or serious adverse drug reactions (sADR), and non-serious AEs (nsAE) or non-serious ADRs (nsADR) occurring within 1 month of IVRz injections were compiled. Results A total of 6404 eyes of 6404 patients received 9406 IVRz injections [mean (± SD) = 1.49 (± 0.63)] during 4.25 years. Adverse events were reported after 1978 injections (21.03%): 64.16% nsAE, 32.96% nsADR, 2.37% sADR, and 0.51% SAE. The most frequent adverse events were subconjunctival hemorrhage (8.2% of total injections), transient blurring of vision (6.5% of total injections), and mild ocular pain (5.27% of total injections). Serious ocular (31 cases with retinal pigment epithelial tears [0.33%], two cases of non-infectious vitritis [0.02%], and one case of endophthalmitis [0.01%]) and systemic (seven patients with non-fatal myocardial infarction [0.12%] and six patients with non-fatal cerebrovascular accident [0.09%]) adverse events were infrequent. Conclusion The study reports the largest pooled safety data on IVRz use in a real-world scenario. The results did not raise any new ocular or systemic safety concerns for the biosimilar agent, with the incidence and spectrum of adverse reactions similar to those reported with other anti-vascular endothelial growth factor (anti-VEGF) drugs. The real-world evidence suggests that IVRz is a safe anti-VEGF agent in the management of chorioretinal disorders. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00345-2.

Purpose The aim of this study was to present the outcomes of the 2018 and 2020 Vitreo-retinal Society of India (VRSI) biosimilars of anti-vascular endothelial growth factor (VEGF) (VIBE) surveys. Methods An online survey of members of VRSI was conducted in July 2018 and January 2020 regarding their practice-patterns on anti-VEGF biosimilars pertaining to safety, efficacy, pricing, and need for enhanced clinical trials before regulatory approval. Results In 2018, 112 VRSI members participated, whereas in 2020, 98 society members participated. In both surveys, majority of respondents were aware of biosimilars (96%, 2018 vs. 100%, 2020; P = 0.9) and felt that approval of biosimilar drugs should be made more stringent with larger clinical trials (89%, 2018 vs. 91%, 2020; P = 0.93). An increase in use of ranibizumab-biosimilar (41%, 2018 to 56%, 2020; P = 0.2) and a simultaneous significant decline in use of bevacizumab-biosimilar (9%, 2018 to 2%, 2020; P = 0.04) was noted from 2018 to 2020. From 2018 to 2020, the proportion of respondents satisfied with safety (61% to 68%; P = 0.59) and efficacy (65% to 81%; P = 0.32) of ranibizumab-biosimilar increased. However, during the same period, we noted in reduction in satisfaction levels with safety of bevacizumab-biosimilar (30% to 25%; P = 0.54), whereas satisfaction with its efficacy was stable (29% vs 30%; P = 0.99). A substantial proportion of retina specialists considered that current cost of ranibizumab-biosimilar ($130) was sufficiently low for it to be used as a substitute for Avastin (37%, 2018 and 40%, 2020; P = 0.82). Conclusion The VRSI surveys reveal that Indian vitreoretinal specialists are familiar with anti-VEGF biosimilars. There was a progressive trend favoring ranibizumab-biosimilar over bevacizumab-biosimilar. One-third of the participants deem the current price of ranibizumab-biosimilar as appropriate to replace Avastin. Simultaneously, the need for enhanced pharmacovigilance and larger clinical trials are warranted for regulatory approval of these agents.

Purpose: Diabetic retinopathy (DR) is the leading cause of blindness among working-aged adults aged 20 to 74 years. Despite professional association guidelines that recommend yearly screening for DR, only about 60% of Americans with diabetes mellitus (DM) receive annual examinations. The purpose of this 2-phase study was to determine the ability of family medicine (FM) physicians to accurately interpret retinal images of patients with DM. Methods: Five FM physicians received a 1-hour lecture on DR by a retinal specialist after which the physicians were shown 30 ultrawide-field retina images and asked to determine whether the images contained signs of DR (phase 1). Patients: Patients with DM who had not received an eye examination within the past year underwent nonmydriatic retinal photography in a FM clinic (phase 2). The 5 FM physicians were asked to evaluate the images for signs of DR and the images were simultaneously sent to a retinal specialist for independent interpretation. The diagnoses of the FM physicians and retina specialist were compared. Patients were informed of their results and were asked to complete a brief telephone survey regarding their experience with the screening process. Results: Thirty retina images, 5 with DR and 25 without DR, were included in the postlecture assessment. Each of the 30 images was reviewed by all 5 FM physicians. Of the 5 images with DR, 3 were correctly diagnosed by all 5 FM physicians, 1 was correctly diagnosed by 4, and 1 was accurately diagnosed by 3. Overall accuracy for the 5 FM physicians was 100%, 100%, 100%, 97%, and 87%. Among the 34 patients included in phase 2, 3 (8%) were diagnosed with DR by the retinal specialist but 8 (24%) were diagnosed with DR by the FM physicians. Of the 3 patients with DR confirmed by the retinal specialist, only 1 was detected by the FM physicians (sensitivity, 33%; 95% CI, 1% to 91%). Of the 31 patients without DR as determined by the retinal specialist, 24 were accurately diagnosed by the FM physicians (specificity, 77%; 95% CI, 59% to 90%). The screening procedure was considered easy/efficient by 28 of 31 (90%) respondents. Conclusion: To improve early detection of DR new screening methods should be considered. FM physicians were able to accurately identify DR on postlecture images but were not as accurate when evaluating images taken from patients in the FM clinic. Patients found the screening process to be easy and efficient. This study was limited by the small sample size, particularly the limited number of DR cases. Future studies that include cases with a wide variation of DR severity are needed to determine the accuracy of FM physicians at detecting DR in a clinical setting.

To determine if routinely performed computed tomographic (CT) scanning in patients with aneurysmal subarachnoid hemorrhages (aSAHs) is sufficient to identify patients at high risk of vision loss due to Terson syndrome (TS).Consecutive patients with a diagnosis of aSAH admitted to the neurologic intensive care unit of a regional referral hospital over a 3-year period were prospectively evaluated. Head CT scans performed in the emergency department were assessed for the presence of a "crescent sign" (evidence of significant subinternal limiting membrane hemorrhage). Dilated funduscopic examinations were performed by an ophthalmologist, masked to the results of the CT scan, to identify retinal and vitreous hemorrhages consistent with TS. Retinal hemorrhages were categorized according to size-those smaller than 2 mm in diameter were deemed low risk (lrTS) for vision loss and those larger than 2 mm in diameter were deemed high risk (hrTS) for vision loss.One hundred seventeen patients with aSAH were enrolled in the study. The overall incidence of TS was 24.9% (29 of 117 patients; 12 were bilateral). Compared to patients without TS, those with TS had a higher Fisher Hemorrhage Grade and a lower mean (±standard deviation) GCS score (8.66 ± 4.97 vs 12.09 ± 1.10; P0.001). The CT crescent sign was positive in 7 patients (6.0%), 6 (5.1%; 2 were bilateral) of whom were found to have hrTS. Of the 110 patients without a CT crescent sign, 88 (75.1%) patients did not have TS, 21 had lrTS, and 1 patient had hrTS in one eye. The CT crescent sign was highly sensitive (85.7%) and specific (99.1%) for diagnosing hrTS.The CT crescent sign is a highly sensitive and specific marker for hrTS. CT scanning may replace routine ophthalmologic examinations to identify patients at risk of vision loss due to aSAH.

Purpose To comprehensively review the literature regarding recurrent corneal erosion (RCE) and to present treatment options and recommendations for management. Overview RCE usually presents with sharp, unilateral pain upon awakening, in an eye with an underlying basement membrane dystrophy, prior ocular trauma, stromal dystrophy or degeneration, or prior surgery for refractive errors, cataracts, or corneal transplantation. Making the correct diagnosis requires a careful slit-lamp examination of both eyes coupled with a high degree of suspicion. Several treatments are commonly used for RCE but new therapies have been introduced recently. Conservative treatment consists of antibiotic and preservative-free lubricating drops, with topical cycloplegics and oral analgesics to control pain. Patients who are unresponsive to these therapies may benefit from therapeutic bandage contact lenses (BCL). Newer therapies include oral matrix metalloproteinase (MMP) inhibitors, blood-derived eye drops, amniotic membrane graft application, and judicious application of topical corticosteroids. Once the epithelium is healed, a course of hypertonic saline solution and/or ointment can be used. Surgical procedures may be performed in patients who fail conservative therapy. Punctal occlusion with plugs increases the tear film volume. Epithelial debridement with diamond burr polishing (DBP), anterior stromal puncture (ASP), or alcohol delamination should be considered in selected patients. DBP can be used for patients with basement membrane dystrophies and is the preferred treatment overall due to a low recurrence rate. ASP can be used for erosions outside the central visual axis. Excimer laser phototherapeutic keratectomy is an attractive option in eyes with central RCE since it precisely removes tissue while preserving corneal transparency. In patients with RCE who are also candidates for refractive surgery, photorefractive keratectomy can be considered. Summary Newly introduced therapies for RCE enable therapy to be individualized and lower the recurrence rate.

Patient: Female, 44 Final Diagnosis: Optic neuritis Symptoms: Unilateral vision loss Medication: — Clinical Procedure: Fundoscopic examination Specialty: Ophthalmology Objective: Rare disease Background: Systemic lupus erythematosus (SLE) causes sight-threatening, ophthalmologic problems that are frequently challenging to manage. Optic neuropathy is a rare ophthalmological complication of SLE that can progress to total bilateral vision loss if not identified and treated rapidly. We describe a patient with SLE who presented with an acute, painless unilateral optic neuropathy who subsequently experienced partial recovery of vision when treated with high-dose intravenous corticosteroids. Case Report: A 44-year-old female with known SLE presented with 4 days of painless, complete, and gradual vision loss in the right eye. Initial ophthalmologic examination revealed no light perception, afferent pupil defect, 4+ optic disc swelling, and 1+ venous tortuosity of the right eye. No hemorrhage or exudates were noted. Diagnostic workup revealed a lupus flare with elevated inflammatory markers including elevated anti-nuclear antibody, anti-ds-DNA antibody, anti-Sm antibody, and anti-phospholipid IgG antibody. The diagnosis of optic neuropathy was clinically established, and the patient was treated with high-dose intravenous corticosteroids. Her vision improved, and she was transitioned to oral corticosteroids with eventual significant improvement in her vision. Conclusions: Optic neuropathy is a rare and devastating ophthalmologic complication of SLE. The diagnosis can be made by linking key clinical findings on ophthalmologic examination with positive serological studies. If treated rapidly with immunosuppressive therapy, the vision loss can be reversed, and permanent blindness avoided. Although this rare complication is generally bilateral in nature, clinician must also be aware of unilateral disease and treat patients accordingly.

Purpose To investigate whether vascular endothelial growth factor (VEGF)-suppression durations contribute to our understanding of clinical trial outcomes by simulating vitreous molar concentrations (Cvm) of intravitreal aflibercept (IVT-AFL) and brolucizumab (IVT-BRO) using pharmacokinetic (PK) modeling. Methods A PK model simulated Cvm after single-dose IVT-AFL, IVT-BRO, and ranibizumab (IVT-RAN), and extrapolated intraocular VEGF-suppression thresholds and durations. Vitreous PK after multidose regimens used in studies of IVT-AFL versus IVT-BRO were simulated and compared with best-corrected visual acuity (BCVA) data. Results Cvm peaked higher (Cmax) and decreased more quickly to the VEGF-suppression threshold and minimum (Cmin) levels with IVT-BRO than with IVT-AFL, consistent with their molar doses calculated using molecular weights and vitreous half-lives (26 kDa and 115 kDa; 4.4-5.1 and 9.1-11 days, respectively). The mean VEGF suppression durations were 71 days for IVT-AFL 2 mg and 51 (48-59) days for IVT-BRO 6 mg. Based on dosing in OSPREY (matched dosing to week [w]32 for both agents; thereafter, IVT-AFL every eight weeks [q8w] and IVT-BRO q12w for the last two doses [w32→w44 and w44→w56]), IVT-BRO showed wider Cmax-Cmin fluctuations than IVT-AFL. The IVT-BRO Cmin fell below the VEGF-suppression threshold at timepoints near w56, when decreases in BCVA were also observed. The IVT-AFL vitreous Cmin remained above the suppression threshold through w56, where BCVA gains were maintained. Conclusions The PK-modeled mean VEGF-suppression duration for IVT-BRO was substantially shorter than that published for IVT-AFL and may not be sufficient to effectively suppress VEGF throughout q12w dosing. Translational relevance The PK modeling suggests that more patients may be maintained on ≥q12w dosing with IVT-AFL than with IVT-BRO.

Introduction: Retinal microvascular abnormalities have been associated with stroke, but their association with dementia and death is less well described. We tested the hypothesis that retinopathy is associated with stroke, dementia, and age-adjusted mortality. Methods: Data were obtained from the US National Health and Nutrition Examination Surveys from 2005 to 2008, with linked mortality through 2015. Severity of retinopathy was defined as no retinopathy, mild nonproliferative retinopathy (NPR), moderate-severe NPR, and proliferative retinopathy. Logistic regression models were performed to evaluate the relationships between retinopathy, stroke, and dementia, respectively. Independent relationships between retinopathy and all-cause mortality were assessed using Cox regression models, before and after adjusting for covariates. All analyses were adjusted for the complex survey design. Results: Of 5,543 participants aged ≥18 years with gradable retinal imaging, 696 had retinopathy, 289 had stroke, and 597 had dementia. Mean age of subjects was 56.3 ± 11.7 years. Retinopathy was associated with higher risk of stroke (adj OR 2.39, P P =0.005). Over a median duration of 118 months (IQR 111-125), there was a dose-dependent relationship between severity of retinopathy and all-cause mortality (adjusted hazard ratios were 1.0, 1.5, 2.4, 3.4 across retinopathy severity; P =0.021). The Figure shows the age-adjusted cumulative mortality curves by retinopathy severity. Conclusions: Participants with retinopathy have a greater than 2-fold increase in stroke risk and a 1.7-fold increase in dementia risk. Having more severe retinopathy confers a higher risk of death after adjusting for age and vascular risk factors. The retina may serve as a tissue biomarker in intervention trials for cerebrovascular and neurodegenerative diseases.

Purpose To report a case of post-operative endophthalmitis following combined cataract extraction and minimally invasive glaucoma surgery with placement of the iStent drainage device. Observation An 87-year-old woman with a nuclear sclerotic cataract and primary open angle glaucoma underwent elective phacoemulsification cataract extraction with iStent placement. Surgery was complicated only by the inability to properly place the second iStent despite several attempts. At 4 days post-operatively she was diagnosed with endophthalmitis. Despite the prompt intravitreal injections of broad spectrum antibiotics, she lost all perception of light. Cultures of anterior chamber aspirates failed to identify a causative organism. Conclusion and importance In what we believe to be the first report of endophthalmitis associated with placement of the iStent, complete loss of vision occurred. Surgeons need to be aware that iStent placement may be complicated by severe endophthalmitis.

Ophthalmologists frequently face patients who refuse asepsis protocols involving povidone-iodine (PI) due to claims of an allergy to iodine. Such patients usually base this claim on previous reactions to shellfish consumption or to imaging procedures that used iodine-based contrast agents. Allergy to iodine, however, is biologically impossible, and iodine deficiency causes severe developmental problems, including mental retardation. Furthermore, shellfish allergy is due to tropomyosins in muscle tissue, and reactions to intravascular contrast dyes are due to hyperosmolar solutions; neither "allergy" is due to iodine. PI, which contains 9-12% iodine, is the preferred antiseptic for ophthalmic procedures. Experience shows that PI can be administered safely to patients claiming iodine allergy. True allergy to PI is rare and, if indicated, skin patch testing can be performed prior to surgery. Patients who react adversely to highly concentrated (5-10%) PI usually experience toxicity to the corneal and conjunctival epithelium after topical administration. Dilute (0.1-0.25%) PI kills microbes quicker than higher concentrations but for shorter periods of time because the total dose of iodine is smaller. Repeated administration (every 20-30 s) of dilute PI effectively kills microbes for as long as necessary with little risk of epithelial toxicity.

Chorioretinal vascular conditions are among the leading causes of blindness throughout the developed world. Patients usually lose vision because of breakdown of the blood-retinal barrier or complications of neovascularization, two consequences of angiogenesis. These pathophysiologic processes are driven by chemokines and cytokines (particularly vascular endothelial growth factor (VEGF)), which are upregulated by vascular and inflammatory damage to fragile tissues. For the past 15 years, the preferred treatment of these conditions has been the intravitreal injection of corticosteroids and drugs that inhibit the actions of VEGF. After intravitreal depot injections, anti-VEGF drugs reconstitute the blood-retinal barrier and inhibit the growth of neovascular complexes while causing significant vascular remodeling. Ranibizumab, aflibercept, and brolucizumab have been approved by the US FDA for the treatment of macular degeneration, whereas bevacizumab is often injected off-label. After intraocular injections, these drugs move through the vitreous and retina according to their size and charge until they bind VEGF and prevent its activation of trans-membrane receptors. The drugs are not metabolized within the eye, they exit primarily through the trabecular meshwork, and they are removed from the systemic circulation via the liver and kidneys. Anti-VEGF drug developers are presently focused on extending the duration of VEGF inhibition with port (reservoir) delivery systems, encapsulated cell technology, nanoparticle technology, and gene therapy. Though several drugs have shown early promise, some have failed to produce an adequate clinical response, and none has successfully completely phase III trials.

PurposeTo quantify differences in the age, gender, race, and clinical complexity of Medicare beneficiaries treated by ophthalmologists and optometrists in each of the United States.DesignCross-sectional study based on publicly accessible Medicare payment and utilization data from 2012 to 2017.MethodsFor each ophthalmic and optometric provider, demographic information of treated Medicare beneficiaries was obtained from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services (CMS) for the years 2012 to 2017. Clinical complexity was defined using Hierarchical Condition Category (HCC) coding.ResultsFrom 2012 to 2017, ophthalmologists in every state treated significantly older beneficiaries, with the greatest difference (4.99 years in 2014) between provider groups seen in Rhode Island. In most states, there was no gender difference among patients treated by the providers, but in 46 states ophthalmologists saw significantly more racially diverse groups of beneficiaries. HCC risk score analysis demonstrated that ophthalmologists in all 50 states saw more medically complex beneficiaries and the differences were statistically significant in 47 states throughout all six years.ConclusionsAlthough there are regional variations in the characteristics of patients treated by ophthalmologists and optometrists, ophthalmologists throughout the United States manage older, more racially diverse, and more medically complex Medicare beneficiaries.

AimTo study the macular structure and vasculature in consecutive nanophthalmic eyes using optical coherence tomography angiography.MethodsThis is a prospective, multicentre, cross-sectional study of patients with nanophthalmos (one or both eyes). The superficial and deep foveal avascular zones (FAZ) were measured both manually and with the machine’s built-in automated measurement tool. Correlations between best corrected visual acuity (BCVA), central macular thickness (CMT) and subfoveolar choroidal thickness (SFCT) were calculated.ResultsSixty-five eyes of 35 subjects (16 men and 19 women) with a mean age of 37.4 years were analysed. The mean±SD of refractive error was 14.3±3.2 dioptres, axial length was 16.4±1.6 mm, CMT was 410.2±128.3 µm and SFCT was 450.1±108.3 µm. FAZ was unmeasurable small size in both the superficial and deep capillary plexus in all eyes, along with tortuosity of the superficial foveal capillaries and large vessels. Foveal folds were present in 29 eyes. Disc drusen was detected in 27 eyes and was absent in 31 eyes, while fundus autofluorescence was positive in 17 and negative in 24 eyes. BCVA varied from 20/20 to 20/800, with a mean of 20/76. Using Spearman’s correlation, logarithm of the minimum angle of resolution BCVA correlated negatively with axial length (r=−0.30; p=0.015).ConclusionsFAZ attenuation, capillary tortuosity, foveal folds and thickened subfoveal choroid characterise the nanophthalmic macula. These findings may result from a redundant retina and the absence of apoptotic foveolar retraction because of developmental arrest of the optic vesicle after closure of the embryonic fissure.

PurposeTo analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ) therapy for various retinal conditions.MethodsThis was a retrospective, observational study which included patients from 14 participating centres who received IVZ. The medical records of patients who received IVZ from March 2015 through October 2017 were evaluated. Patient demographics and ocular details were compiled. Ocular and systemic adverse events that occurred within 1 month of IVZ injections were recorded and defined as either procedure-related or drug-related.ResultsA total of 1704 eyes of 1562 patients received 5914 IVZ injections (mean±SD: 3.73±3.94) during a period of 2.5 years. The age of patients was 60.6±12.8 years (mean±SD) and included diverse chorioretinal pathologies. Both ocular (one case of endophthalmitis, three cases of intraocular inflammation, and one case each of conjunctival thinning/necrosis and scleral nodule) and systemic adverse events (two cases of myocardial infarction, one case of stroke and two deaths) were infrequent.ConclusionThis constitutes the largest pooled safety report on IVZ use and includes patients from 14 centres distributed across the globe. It shows that IVZ has an acceptable ocular and systemic safety profile with incidences of adverse events similar to those of other vascular endothelial growth factor inhibitory drugs. The analysis supports the continued use of IVZ in various retinal disorders.

Post-operative endophthalmitis (POE) following cataract surgery is an uncommon, vision-threatening complication that has been reported to occur at rates of between approximately 0.03% and 0.2%. Prompt diagnosis and treatment of endophthalmitis is critical for minimizing vision loss, but most recent efforts have focused on the prophylactic administration of antibiotics to prevent the development of endophthalmitis. Surgeons from around the world have different topical and intracameral antibiotic usage patterns to prevent endophthalmitis, and to date no general consensus regarding best practice has emerged. Several studies have reported on the routine use of intracameral cefuroxime, moxifloxacin, and vancomycin, including a single randomized clinical trial by the European Society of Cataract and Refractive Surgery (ESCRS) in 2007. These studies have notable shortcomings, but many authors suggest that intracameral cefuroxime together with topical antibiotics probably decreases the risk of endophthalmitis. However, the deleterious effects of routine prophylactic antibiotics, which include toxicity, cost, and increasing antimicrobial resistance, among others, are noteworthy. In contrast, aseptic technique with pre-operative instillation of povidone-iodine remains the only technique supported by level I evidence to reduce the incidence of endophthalmitis. Although the routine use of intracameral antibiotics continues to increase throughout the world, data from multicenter, randomized, prospective trials is needed to provide better guidance regarding the prophylactic use of antibiotics.

Purpose To evaluate the effectiveness of orbital radiotherapy (ORT) in the treatment of thyroid eye disease (TED)-compressive optic neuropathy. Methods A retrospective review of patients with corticosteroid-responsive compressive optic neuropathy due to TED treated with ORT. Study was conducted in compliance with Health Insurance Portability and Accountability Act. One hundred four patients (163 orbits) with a mean age of 61.7 years met inclusion criteria. Seventy-four percent (77/104) were female, and 32.7% (34/104) were current or previous smokers. A total absorbed dose of 2000 cGy fractionated in 10 treatment doses over the course of 2 weeks was administered to the retroocular tissues according to a standard protocol. The primary end point was failure of ORT, defined as persistent optic neuropathy following completion of radiotherapy that mandated urgent orbital decompression surgery. Results Ninety-eight of 104 (94%) patients or 152 of 163 (93.3%) orbits did not require orbital decompression surgery during the acute phase. Patients who responded successfully to ORT had similar improvements in visual acuity, color vision, Humphrey threshold visual field testing, and afferent pupillary defects compared with patients who failed ORT and underwent urgent decompression surgery. Only 36.7% of successfully treated patients ultimately underwent elective surgery, including orbital decompression, strabismus, or eyelid surgery, during the inactive phase of TED. Conclusions The data from this study, the largest retrospective review reported to date, supports the use of ORT in eyes with corticosteroid-responsive TED-compressive optic neuropathy. ORT may favorably alter the natural history of active-phase TED by preventing recurrent compressive optic neuropathy after withdrawal of corticosteroids.

Twenty-five percent of diabetes-related vision loss stems from complications of proliferative diabetic retinopathy (PDR). Panretinal photocoagulation has been the preferred treatment of high-risk PDR for decades and more recently intravitreal injections of drugs that inhibit the actions of vascular endothelial growth factor have become popular. But despite these treatments PDR may progress uncontrollably to advanced pathologies such as traction retinal detachments (TRDs), combined traction/rhegmatogenous retinal detachments (TRD/RRDs), vitreous hemorrhages, rubeosis iridis, and traction maculopathies, which produce mild-to-severe loss of vision. TDR have long been the most common indication for PDR-related vitreoretinal surgery. Vitrectomy surgery is indicated for recent (6 months duration) may also benefit. Combined TRD/RRD represents a particularly challenging surgical condition but advances in surgical instrumentation, dissection techniques, and post-operative tamponade have produced excellent success rates. The recent development of small-gauge vitrectomy systems has persuaded most surgeons to switch platforms since these appear to produce shorter surgical times and quicker post-operative recoveries. Pre-operative injections of bevacizumab are frequently administered for persistent neovascularization to facilitate surgical dissection of pre-retinal fibrosis and reduce the incidence of post-operative hemorrhages. Recent trends toward earlier surgical intervention and expanded indications are likely to continue as surgical instrumentation and techniques are further developed.

Purpose: To determine the predictive values of baseline optical coherence tomography (OCT) abnormalities on 12-month visual acuity changes in eyes with macular edema (ME) caused by branch retinal vein occlusions (BRVO). Methods: We performed a post hoc analysis of data from 75 participants in the 12-month MARVEL trial. OCT abnormalities at baseline, including ganglion cell layer cystoid spaces (GCL), intraretinal hyper-reflective dots, and central subfield thickness (CST), were correlated with improvements in visual acuity and the number of anti-vascular endothelial growth factor injections required using a multivariate regression model. Results: Eyes with baseline CST > 500 μm had greater visual gains compared to those with CST

Diabetic macular oedema (DMO) is the leading cause of vision loss in working aged individuals. Macular laser photocoagulation was the primary DMO treatment for several decades, but has recently been replaced by intravitreal injections of corticosteroids and drugs that inhibit the actions of vascular endothelial growth factor (VEGF). In Phase III trials, anti-VEGF drugs improve best corrected visual acuity by a mean of +12 letters, but up to 40% of patients have sub-optimal responses to therapy. The new anti-VEGF drugs abicipar and brolucizumab may possess extended durations of action in Phase III neovascular age-related macular degeneration trials, and DMO trials are being planned. Angiopoietin-2 inhibitors, both as co-formulations with anti-VEGF drugs and as bispecific antibodies, are in Phase II trials for DMO. Drugs that stimulate the Tie2 receptor are administered via subcutaneous injections. Intravenously administered antibodies that decrease diabetes-mediated inflammation, such as tocilizumab and teprotumumab, are entering early phase studies. Other drugs with topical (mecamylamine) and oral (minocycline) delivery routes are being developed. Several of these drugs may become available to patients within the next 5–10 years.

Ziv-aflibercept (Zaltrap® ), a recombinant fusion protein that binds diffusible vascular endothelial growth factor (VEGF), is approved for the treatment of metastatic colorectal carcinoma. Its molecular structure is the same as aflibercept (Eylea® ), thus making it an attractive option for the off-label treatment of chorioretinal vascular conditions. Ziv-aflibercept is distributed in 4 and 8 ml vials for intravenous use, and its cost after compounding is similar to bevacizumab. Studies with retinal pigment epithelium cytotoxicity, animal histologic sections and electroretinography have demonstrated its safety, and mathematical modelling combined with over four dozen clinical publications from different ophthalmic centres throughout the world attest to its efficacy. No appreciable differences in visual or anatomic outcomes between 1.25 mg (0.05 ml) and 2.5 mg (1.0 ml) doses have been noted. The long duration of action combined with the low cost make ziv-aflibercept an attractive anti-VEGF treatment option, especially in low- and middle-income countries where its popularity is increasing.

Purpose To comprehensively review the literature regarding recurrent corneal erosion (RCE) and to present treatment options and recommendations for management. Overview RCE usually presents with sharp, unilateral pain upon awakening, in an eye with an underlying basement membrane dystrophy, prior ocular trauma, stromal dystrophy or degeneration, or prior surgery for refractive errors, cataracts, or corneal transplantation. Making the correct diagnosis requires a careful slit-lamp examination of both eyes coupled with a high degree of suspicion. Several treatments are commonly used for RCE but new therapies have been introduced recently. Conservative treatment consists of antibiotic and preservative-free lubricating drops, with topical cycloplegics and oral analgesics to control pain. Patients who are unresponsive to these therapies may benefit from therapeutic bandage contact lenses (BCL). Newer therapies include oral matrix metalloproteinase (MMP) inhibitors, blood-derived eye drops, amniotic membrane graft application, and judicious application of topical corticosteroids. Once the epithelium is healed, a course of hypertonic saline solution and/or ointment can be used. Surgical procedures may be performed in patients who fail conservative therapy. Punctal occlusion with plugs increases the tear film volume. Epithelial debridement with diamond burr polishing (DBP), anterior stromal puncture (ASP), or alcohol delamination should be considered in selected patients. DBP can be used for patients with basement membrane dystrophies and is the preferred treatment overall due to a low recurrence rate. ASP can be used for erosions outside the central visual axis. Excimer laser phototherapeutic keratectomy is an attractive option in eyes with central RCE since it precisely removes tissue while preserving corneal transparency. In patients with RCE who are also candidates for refractive surgery, photorefractive keratectomy can be considered. Summary Newly introduced therapies for RCE enable therapy to be individualized and lower the recurrence rate.

The development and widespread adoption of drugs that inhibit the actions of vascular endothelial growth factor (VEGF) have transformed the treatment of chorioretinal vascular conditions during the...

AimTo describe an extensive scleral excision technique to treat uveal effusion in nanophthalmic eyes.MethodsThis prospective, interventional series of eight eyes of five consecutive patients with nanophthalmos underwent scleral window surgeries. Ninety per cent of the scleral thickness, extending from immediately behind the extraocular muscle insertions to the vortex veins for 3 and 1/4 quadrants, was removed. The main outcome measure was resolution of the uveal effusions.ResultsEight eyes of five patients (one female and four male) with a mean age of 46 years were studied. The mean (range) axial length was 16.1 mm (14.6–17.6 mm), and the mean refractive error was +13.6 dioptres (+10.75 to +16.00 dioptres). Following scleral excision surgery, all uveal effusions resolved within an average (±SD) of 13.9 (±8.7) days. The uveal effusion recurred in only one eye that had a vasoproliferative retinal tumour. The mean best corrected visual acuity improved from 0.69 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent: 20/97) at baseline to 0.51 logMAR (Snellen equivalent: 20/64; Wilcoxon paired t-test: p=0.016) after a mean follow-up of 35.6 months.ConclusionThe circumferential scleral window technique produces rapid resolution of uveal effusion in nanophthalmic eyes. No adverse effects were noted after surgery and the clinical effect was durable through 1 year.Trial registration numberNCT03748732.

Chorioretinal vascular diseases are among the leading causes of blindness in industrialised countries. The recent development and widespread adoption of intravitreal pharmacotherapy enables surgeons to not only stabilise disease in most cases, but also improve visual acuity (VA). Inhibitors of vascular endothelial growth factor (VEGF) have become first-line therapy for patients with neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO), and oedema due to retinal vein occlusions (RVO). The pivotal Phase III registration studies evaluated the efficacy and safety of monthly or bimonthly injections of anti-VEGF drugs, and remain the standard against which other treatments and injection regimens are compared. Adhering to a regimen of monthly drug injections requires considerable patient compliance and allocation of substantial healthcare resources, therefore most physicians use individualised treatment strategies. As-needed (PRN) and treat and extend (T&E) regimens reduce the number of clinic visits, intravitreal injections, or both, and are less expensive than monthly therapy. Both regimens reduce unwanted macular oedema and improve VA, but compared to monthly therapy over the course of 1 year, may be 1–3 letters less effective. Trials of 5-year duration suggest that PRN treatment modulates the severity of diabetic retinopathy (DR) and stabilises vision in patients with DR. Long-term data comparing these strategies in patients with nAMD and RVO are lacking, but VA frequently declines when observation periods and treatment intervals are extended beyond 4 weeks. Current observations suggest that aggressive long-term therapy with frequent injections may produce the best VA results in patients with nAMD and RVO.

Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first-line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME.

Zahid Syed,1 Michael W Stewart2 1Georgetown University, Washington, DC, 2Department of Ophthalmology, Mayo School of Medicine, Jacksonville, FL, USA Background: Vitreous degeneration begins soon after birth and accelerates throughout life. Vitreous liquefaction with a slowly progressive separation of the posterior hyaloid from the peripheral macula usually leads to complete posterior vitreous detachment. The purpose of this study is to measure the age-related prevalence of partial vitreous separation and the length of residual vitreous adhesion in an ophthalmology clinic population. Methods: Patients examined by the senior author (MWS) during a 6-month period were included in a retrospective chart review. Demographic data and spectral domain optical coherence tomography scan results were gathered. Data analysis with descriptive statistics focused on the prevalence and extent of partial vitreous separation. Results: The mean age of the study patients was 69.9years, and 62% were phakic. The highest prevalence of partial posterior hyaloid separation from the internal limiting membrane (71.2%) was seen in the 50- to 54-year age group. This prevalence rate steadily decreased to 5.6% in the 95- to 99-year age group. The prevalence of complete vitreous detachment as determined by slit-lamp biomicroscopy increased from 1.7% in the

AIM To evaluate the safety of intravitreal ziv-aflibercept (Zaltrap) in the treatment choroidal neovascularization secondary to age-related macular degeneration. METHODS Eligible eyes with choroidal neovascularization secondary to age-related macular degeneration each received a single intravitreal injection of ziv-aflibercept. Comprehensive ophthalmic examinations and detailed systemic evaluations were performed at baseline and Days 1, 7, and 30 after injection, and International Society for Clinical Electrophysiology of Vision standard electroretinography was performed at baseline and Day 30. Primary outcome measures were safety parameters that included signs of clinical and electroretinographic toxicity. Secondary outcome measures included changes in best-corrected visual acuity and central subfield thickness. RESULTS Twelve eyes of 12 patients were treated. None of the patients complained of blurred vision, ocular pain, or bulbar injection at any of the follow-up visits, nor was intraocular inflammation noted. There were no significant differences in implicit times, "a" and "b" wave amplitudes, or b/a ratios at 1 month when compared with baseline (P = 0.4). None of the patients experienced serious ocular or systemic adverse events. Mean best-corrected visual acuity improved only slightly at 30 days (LogMAR 0.45 ± 0.31 [Snellen equivalent: 20/60]) compared with baseline (LogMAR 0.37 ± 0.24 [Snellen equivalent: 20/50]; P = 0.51). CONCLUSION Single intravitreal injections of ziv-aflibercept into eyes with neovascular age-related macular degeneration appear to be safe through 1 month. Ziv-aflibercept could become a safe, low-cost therapy for macular diseases in developing countries and in those where intravitreal aflibercept (Eylea) is not available.

David J Browning,1 Chong Lee,1 Michael W Stewart,2 Maurice B Landers III3 1Charlotte Eye, Ear, Nose and Throat Associates, Charlotte, NC, 2Mayo Clinic, Jacksonville, FL, 3Kittner Eye Center, University of North Carolina, Chapel Hill, NC, USA Purpose: To determine the effect of vitrectomy for center-involved diabetic macular edema (CI-DME). Methods: This was a retrospective study of 53 eyes of 45 patients who had vitrectomy for CI-DME and were followed up for at least 12months. Charts were reviewed for visual acuity (VA), central subfield mean thickness measured by optical coherence tomography, presurgical and postsurgical interventions for CI-DME, and number of office visits in the first 12months after surgery. Preoperative spectral domain optical coherence tomography was performed on 38 patients, and they were graded for ellipsoid zone (EZ) intactness by three independent graders with assessment of agreement between graders using intraclass correlation coefficients and Bland–Altman analysis. Results: The median VA improved from 20/100 (interquartile range [IQR], 20/63–20/200) at baseline to 20/63 (IQR, 20/32–20/125) at 12months. The median central subfield mean thickness improved from 505µm (IQR, 389–597µm) at baseline to 279µm (IQR, 246–339µm) at 12months. Intergrader agreement for EZ intactness was moderate (intraclass correlation coefficients 0.4294–0.6356). There was no relationship between preoperative intactness of the EZ and the 12-month change in VA. Conclusion: Vitrectomy consistently thins the macula in CI-DME and, on average, leads to clinically significant improvement in VA comparable in size to that reported with serial intravitreal anti-vascular endothelial growth factor injections. A large, comparative, prospective, randomized clinical trial of these two treatments is needed to determine which is more effective and cost-effective. Keywords: center-involved diabetic macular edema, diabetic macular edema, vitrectomy, spectral domain OCT