The impact of artificial intelligence on retinal disease management: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The aim of this review is to define the "state-of-the-art" in artificial intelligence (AI)-enabled devices that support the management of retinal conditions and to provide Vision Academy recommendations on the topic. RECENT FINDINGS: Most of the AI models described in the literature have not been approved for disease management purposes by regulatory authorities. These new technologies are promising as they may be able to provide personalized treatments as well as a personalized risk score for various retinal diseases. However, several issues still need to be addressed, such as the lack of a common regulatory pathway and a lack of clarity regarding the applicability of AI-enabled medical devices in different populations. SUMMARY: It is likely that current clinical practice will need to change following the application of AI-enabled medical devices. These devices are likely to have an impact on the management of retinal disease. However, a consensus needs to be reached to ensure they are safe and effective for the overall population.

Current status and practical considerations of artificial intelligence use in screening and diagnosing retinal diseases: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The application of artificial intelligence (AI) technologies in screening and diagnosing retinal diseases may play an important role in telemedicine and has potential to shape modern healthcare ecosystems, including within ophthalmology. RECENT FINDINGS: In this article, we examine the latest publications relevant to AI in retinal disease and discuss the currently available algorithms. We summarize four key requirements underlining the successful application of AI algorithms in real-world practice: processing massive data; practicability of an AI model in ophthalmology; policy compliance and the regulatory environment; and balancing profit and cost when developing and maintaining AI models. SUMMARY: The Vision Academy recognizes the advantages and disadvantages of AI-based technologies and gives insightful recommendations for future directions.

Assessment of systemic and ocular inflammation in juvenile idiopathic arthritis via choroidal vascularity index.

We aimed to evaluate the retina and the choroid in children with juvenile idiopathic arthritis (JIA) employing optical coherence tomography (OCT). This cross-sectional study, carried out between June 2017-December 2019, included JIA patients with (JIAU; n = 28) and without (JIAN; n = 65) uveitis and age-matched healthy controls (HC) (n = 102). Laboratory and demographic information of the children were obtained from hospital records. Activity of the disease was evaluated by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71). Choroidal scans were obtained with spectral domain-OCT in enhanced-depth imaging (EDI)-OCT mode to assess choroidal thickness (ChT) at five locations (under the fovea, at 750 and 1500 µm nasal and temporal sections), luminal area (LA), stromal area (SA), total subfoveal choroidal area (TCA) and CVI (choroidal vascularity index). Central foveal thickness (CFT) and 1-mm diameter foveal thickness (FT) were calculated automatically through macular volume scan analysis. The choroid was significantly thicker in JIAU and JIAN patients than in HC at the subfoveal and at the 750N, 750T, 1500T points (p < 0.001, p = 0.009, p < 0.001, and p < 0.001, respectively). The CVI was lower in JIAU patients than in JIAN patients and HC (p = 0.02). Conversely, CFT was greater in JIAU patients as compared to the JIAN patients and HC (p = 0.02). Changes in chorioretinal OCT parameters in the absence of uveitis in JIA patients may reflect subclinical choroidal inflammation in these patients. Ophthalmologic examination, including choroidal imaging in a larger cohort, may clarify this aspect.

Nonadherence or Nonpersistence to Intravitreal Injection Therapy for Neovascular Age-Related Macular Degeneration: A Mixed-Methods Systematic Review.

TOPIC: Systematic review of risk factors for nonadherence and nonpersistence to intravitreal anti-vascular endothelial growth factor (VEGF) injection therapy for neovascular age-related macular degeneration (nAMD). CLINICAL RELEVANCE: Lack of adherence (nonadherence) or undertreatment (nonpersistence) with respect to evidence from clinical trials remains a significant barrier to optimizing real-world outcomes for patients with nAMD. Contributing factors and strategies to address this are poorly understood. METHODS: Studies that reported factors for nonadherence and nonpersistence to anti-VEGF therapy as well as studies examining strategies to improve this were included. Trial eligibility and data extraction were conducted according to Cochrane review methods. Risk of bias was assessed using the Mixed Method Assessment Tool and certainty of evidence evaluated according to the GRADE Confidence in the Evidence from Reviews of Qualitative Research tool. Data were collated descriptively. RESULTS: Of the 1284 abstract results screened, 124 articles were assessed in full and 37 studies met the inclusion criteria. Definitions of nonadherence and nonpersistence varied or were not reported. Nonpersistence occurred early, with up to 50% of patients stopping treatment by 24 months. High rates of nonadherence were similarly reported, occurring in 32% to 95% of patients. Certainty of this finding was downgraded to a moderate level because of the heterogeneity in definitions used across studies. Multiple factors determine nonadherence and nonpersistence, including at the condition, therapy, patient, social/economic, and health systems/healthcare team levels. Moderate quality evidence points to lower baseline vision and poorer response to treatment as condition-related variables. The effects of other factors were of lower certainty, predominantly due to small numbers and potential biases in retrospective assessment. Although many factors are not modifiable (e.g., patient comorbidity), other factors are potentially correctable (e.g., lack of transport or mismatched patient expectations). Evidence on strategies to improve adherence and persistence is limited, but where available, these have proven effective. CONCLUSIONS: Awareness of factors related to poor patient adherence and persistence in nAMD could help identify at-risk populations and improve real-world outcomes. Further work is required to develop uniform definitions and establish high-quality evidence on interventions that can be easily implemented.

Anti-VEGF intravitreal injections in the era of COVID-19: responding to different levels of epidemic pressure.

PURPOSE: Following the first wave of the COVID-19 pandemic in early 2020, the easing of strict measures to reduce its spread has led to a resurgence of cases in many countries at both the national and local level. This article addresses how guidance for ophthalmologists on managing patients with retinal disease receiving intravitreal injections of anti-vascular endothelial growth factor (VEGF) during the pandemic should be adapted to the local epidemic pressure, with more or less stringent measures implemented according to the ebb and flow of the pandemic. METHODS: The Vision Academy's membership of international retinal disease experts analyzed guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic and graded the recommendations according to three levels of increasing epidemic pressure. The revised recommendations were discussed, refined, and voted on by the 14-member Vision Academy Steering Committee for consensus. RESULTS: Protocols to minimize the exposure of patients and healthcare staff to COVID-19, including use of personal protective equipment, physical distancing, and hygiene measures, should be routinely implemented and intensified according to local infection rates and pressure on the hospital/clinic or healthcare system. In areas with many COVID-19-positive clusters, additional measures including pre-screening of patients, postponement of non-urgent appointments, and simplification of complex intravitreal anti-VEGF regimens should be considered. Treatment prioritization for those at greatest risk of irreversible vision loss should be implemented in areas where COVID-19 cases are increasing exponentially and healthcare resources are strained. CONCLUSION: Consistency in monitoring of local infection rates and adjustment of clinical practice accordingly will be required as we move forward through the COVID-19 era. Ophthalmologists must continue to carefully weigh the risk-benefits to minimize the exposure of patients and healthcare staff to COVID-19, ensure that patients receive sight-saving treatment, and avoid the potential long-term impact of prolonged treatment postponement.

Guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic.

PURPOSE: There is an urgent need to address how to best provide ophthalmic care for patients with retinal disease receiving intravitreal injections with anti-vascular endothelial growth factor agents during the ongoing global COVID-19 pandemic. This article provides guidance for ophthalmologists on how to deliver the best possible care for patients while minimizing the risk of infection. METHODS: The Vision Academy's Steering Committee of international retinal disease experts convened to discuss key considerations for managing patients with retinal disease during the COVID-19 pandemic. After reviewing the existing literature on the issue, members put forward recommendations that were systematically refined and voted on to develop this guidance. RESULTS: The considerations focus on the implementation of steps to minimize the exposure of patients and healthcare staff to COVID-19. These include the use of personal protective equipment, adherence to scrupulous hygiene and disinfection protocols, pre-screening to identify symptomatic patients, and reducing the number of people in waiting rooms. Other important measures include triaging of patients to identify those at the greatest risk of irreversible vision loss and prioritization of treatment visits over monitoring visits where possible. In order to limit patient exposure, ophthalmologists should refrain from using treatment regimens that require frequent monitoring. CONCLUSION: Management of patients with retinal disease receiving intravitreal injections during the COVID-19 pandemic will require adjustment to regular clinical practice to minimize the risk of exposure of patients and healthcare staff, and to prioritize those with the greatest medical need. The safety of patients and healthcare staff should be of paramount importance in all decision-making.

CURRENT CONCEPTS AND MODALITIES FOR MONITORING THE FELLOW EYE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: An Expert Panel Consensus.

PURPOSE: The presence of neovascular age-related macular degeneration (nAMD) in one eye is a major risk factor for the development of disease in the fellow eye. Several methods exist to help physicians monitor the fellow eye, with new technologies becoming increasingly available. METHODS: We provide an overview of modalities for nAMD monitoring, including advances in home-based options, and review their utility for fellow-eye monitoring, based on a review of the literature and a consensus of retinal experts. RESULTS: Studies demonstrate the importance of early detection of nAMD in the fellow eye so that interventions can be made before significant vision loss occurs. A series of techniques exist for the early detection of nAMD including chart-based methods and imaging devices. The increased availability of home-based methods has presented an opportunity for patients to monitor their vision at home. CONCLUSION: Frequent monitoring of the fellow eye in patients with unilateral nAMD is of critical importance to prevent vision loss and maintain quality of life. Patients should be examined every 3 to 4 months from the time of choroidal neovascularization diagnosis and encouraged to monitor their vision at home using home-based technologies where available, to provide the best opportunity for early detection.

Anti-vascular endothelial growth factor in neovascular age-related macular degeneration - a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems.

BACKGROUND: Systematically review the evidence describing the impact of anti-vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization. METHODS: A systematic literature review was completed using Medline and EMBASE for publications prior to July 2018, and proceedings from major ophthalmology conferences (January 2016 to July 2018). The search strategy combined terms for nAMD with terms for anti-VEGF and study design. The review focused on publications describing the impact of anti-VEGF on blindness, visual impairment, vision-related quality of life (VRQoL), mortality, and costs. The search targeted data collected in epidemiological or observational studies to reflect real-world outcomes but also considered modeling-based approaches. RESULTS: The use of anti-VEGF in clinical practice was associated with significant reduction in the incidence of blindness by nAMD. Population-based analyses reported reduction in incidence among the general population of 47% (9.1 cases/100,000 in 2006 to 4.8 cases/100,000 in 2011). Among patients aged ≥50 years, a reduction of 50% was observed (52.2 cases/100,000 in 2000 to 25.7 cases/100,000 in 2010). In some cases, the odds of decreased vision (defined as decline from normal to moderate, moderate to severe, or severe to blindness) fell by 41% following introduction of anti-VEGF. Patients' VRQoL improved with treatment, with patients reporting a positive impact shortly after treatment was initiated. Change on National Eye Institute 25-Item Visual Function Questionnaire score from baseline to month 12 ranged from 0.7 to 4.4. Although nAMD patients report signs of depression and anxiety, the evidence suggests that there is no association between the use of anti-VEGF and the prevalence or diagnosis of depression. The introduction of anti-VEGF led to increased overall treatment costs due to replacement of existing less frequently administered treatments (e.g. photodynamic therapy) and increased number of patients treated (prior to anti-VEGF, only ~ 20% of patients were eligible for treatment). CONCLUSIONS: The introduction of anti-VEGF agents has been associated with a positive impact on patient-relevant outcomes, including a significant reduction in incidence of blindness and visual impairment by nAMD. Anti-VEGF agents replaced less-effective treatments, improving patient outcomes and broadening the patient population eligible for treatment.

Complement Factor I Gene Polymorphism in a Turkish Age-Related Macular Degeneration Population.

OBJECTIVE: Evaluation of Complement Factor I (CFI) rs10033900 and rs2285714 polymorphism frequencies in patients with age-related macular degeneration (AMD) and healthy controls in a Turkish population. METHODS: A total of 111 eyes of 111 AMD patients and 96 eyes of 96 healthy controls, only one eye of individuals, were included in the study; however, 2 patients' and 4 controls' samples were excluded as analyses could not be performed for rs10033900 polymorphism. The AMD patients and control group (>50 years) lacked corneal, lenticular, vitreal opacity. However, these patients did not have any retinal diseases apart from AMD. Venous blood samples of patients were collected. Central macular thickness, subfoveal choroidal thickness (SCT), presence of reticular drusen, epiretinal membrane, and pigment epithelial detachment were investigated using Spectral-Domain Optical Coherence Tomography, and the largest diameter of atrophic areas measured. Drusen properties were documented from fundus photographs. The lesion width was calculated by using fundus fluorescein angiography. RESULTS: There was no difference between patient and control groups and polymorphism distributions. The frequency of the CT allele was higher in patients with dry-type AMD with retinal pigment epithelial abnormality (p = 0.041). SCT was significantly thinner in TT allele carriers with rs2285714 polymorphism (p = 0.030). No significant relationship was found between the other parameters and polymorphism distributions. Con-clusion: CFI rs10033900 and rs2285714 polymorphisms in a Turkish population were not associated with AMD.

Real-world data in retinal diseases treated with anti-vascular endothelial growth factor (anti-VEGF) therapy - a systematic approach to identify and characterize data sources.

BACKGROUND: Real-world data (RWD) has been a valuable addition to the scientific literature regarding treatment pathways, clinical outcomes and characteristics of patients with retinal diseases in recent years. Registries, observational studies and patient databases are often used for real-world research. However, there is limited information for each data source on the design, consistency, data captured, limitations and usability for assessing research questions. Using a systematic approach, we identified RWD sources for patients with retinal diseases and assessed them for completeness of data relating to different outcomes. METHODS: A systematic literature review was carried out to identify RWD sources for patients with retinal disease. Potentially relevant articles published between 2006 and 2016 were screened following electronic searches in Embase and MEDLINE. Congress and supplementary searches were undertaken to identify RWD sources that may not be referenced in full publications. For each data source, availability and quantity of data on baseline status, clinical outcomes, treatment and management, safety, and patient-reported and economic burden were assessed using a bespoke completeness assessment tool based on International Consortium for Health Outcomes Measurement guidelines for macular degeneration. Completeness of data for each area of interest in each data source was assessed and rated using a 'good-moderate-poor' rating system based on availability and quantity of available data. Each data source was then given an overall score based on its score for each of the 7 areas of interest. RESULTS: A total of 128 RWD sources from 32 countries were identified. Of the identified sources, 64 sources from 16 countries of interest were analyzed. Most of these sources provided information on baseline status and clinical outcomes and treatment, but few collected data on economic and patient-reported burden. Of the RWD sources analyzed, 10 scored highly in the overall completeness assessment, collecting data on most or all of the areas of interest; these sources are considered to be robust data sources for performing ophthalmology real-world studies. CONCLUSIONS: The study provides a comprehensive list of RWD sources for patients with retinal disease, many of which will be useful for conducting real-world studies in the field of ophthalmology.

An analysis of ranibizumab treatment and visual outcomes in real-world settings: the UNCOVER study.

PURPOSE: To describe intravitreal ranibizumab treatment frequency, clinical monitoring, and visual outcomes (including mean central retinal thickness [CRT] and visual acuity [VA] changes from baseline) in neovascular age-related macular degeneration (nAMD) in real-world settings across three ranibizumab reimbursement scenarios in the Middle East, North Africa, and the Asia-Pacific region. METHODS: Non-interventional multicenter historical cohort study of intravitreal ranibizumab use for nAMD in routine clinical practice between April 2010 and April 2013. Eligible patients were diagnosed with nAMD, received at least one intravitreal ranibizumab injection during the study period, and had been observed for a minimum of 1 year (up to 3 years). Reimbursement scenarios were defined as self-paid, partially-reimbursed, and fully-reimbursed. RESULTS: More than three-fourths (n = 2521) of the analysis population was partially-reimbursed for ranibizumab, while 16.4% (n = 532) was fully-reimbursed, and 5.8% was self-paid (n = 188). The average annual ranibizumab injection frequency was 4.1 injections in the partially-reimbursed, 4.7 in the fully-reimbursed and 2.6 in the self-paid populations. The average clinical monitoring frequency was estimated to be 6.7 visits/year, with similar frequencies observed across reimbursement categories. On average, patients experienced VA reduction of -0.7 letters and a decrease in CRT of -44.4 µm. The greatest mean CRT change was observed in the self-paid group, with -92.6 µm. CONCLUSIONS: UNCOVER included a large, heterogeneous ranibizumab-treated nAMD population in real-world settings. Patients in all reimbursement scenarios attained vision stability on average, indicating control of disease activity.

Real-World Results of Intravitreal Ranibizumab, Bevacizumab, or Triamcinolone for Diabetic Macular Edema.

OBJECTIVE: To compare the visual and anatomical outcomes of intravitreal ranibizumab (group 1), bevacizumab (group 2), and triamcinolone (group 3) for center-involving diabetic macular edema. METHODS: We retrospectively enrolled 275 eyes of 208 consecutive patients. Visual acuity (VA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters and central macular thickness (CMT) values on optical coherence tomography were extracted. Reported side effects were noted. RESULTS: At 6 months, the mean changes in VA in group 1, group 2, and group 3 were +4.9, +4.3, and +4.6 letters, respectively (p = 0.911). Improvement of CMT at 6 and 24 months was significantly better in group 3 compared to groups 1 and 2 (p = 0.012 and p = 0.001, respectively). At 24 months, the only independent variable affecting the change in VA was initial VA (p = 0.020). Cataract and glaucoma prevalences were higher in group 3 (p = 0.000 and p = 0.001, respectively). CONCLUSIONS: Three treatment methods had similar effects with regard to improvement in VA; however, intravitreal triamcinolone provided additional anatomical improvement.

The effect of CFH polymorphisms on the response to the treatment of age-related macular degeneration (AMD) with intravitreal ranibizumab.

PURPOSE: The purpose of this study is to evaluate the effect of complement factor H (CFH) Y402H CC and TT polymorphisms on treatment response to intravitreal ranibizumab injection in patients with wet age-related macular degeneration (AMD). METHODS: One hundred ninety-three patients with choroidal neovascularization (CNV) secondary to AMD who were monitored for at least 6 months of follow-up, and with at least three ranibizumab injections, were included in the study. At the final examination, an increase in visual acuity (VA) of five letters or more compared to the initial VA was regarded as a good response, and a decrease in VA of five letters or more compared to the initial VA was evaluated as a poor response. A genetic examination was performed with a PCR melting curve analysis. In the statistical evaluation, SPSS version 18 software was used. RESULTS: The mean age of the patients was 71.01 (55-86) years, the mean follow-up was 13.34 (6-36) months, and the mean number of injections was 4.02 (3-15). There were 96 patients in the good response group (Group 1) and 97 patients in the poor response group (Group 2). The initial VA in Group 1 was 41.34 (10-64) letters, the initial central macular thickness (CMT) was 213.40 (126-494) µm, and the initial lesion width was 3760 (1430-6430) µm. The initial VA in Group 2 was 52.89 (26-82) letters, the initial CMT was 257.60 (115-882) µm, and the initial lesion width was 4460 (1000-7650) µm. There was no statistically significant difference between the two groups in terms of the initial VA and CMT (p=0.094, p=0.083). However, there was a statistically significant difference between the groups in the width of the initial lesion (p=0.003). In Group 1, 15 CC, 30 TT, and 51 TC alleles were found, and in Group 2, 49 CC, two TT, and 46 TC alleles were found, and the distribution was significantly different between the two groups (p=0.012). The change in the distribution of genotypes was not associated with either the lesion size or VA (p=0.841). Fibrosis developed in 12 patients who were all poor responders. CONCLUSIONS: CFH Y402H CC accompanied a poor response, and TT accompanied a good response in this series of patients with AMD undergoing ranibizumab therapy.

The SECURE study: long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration.

OBJECTIVE: To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). DESIGN: Twenty-four-month, open-label, multicenter, phase IV extension study. PARTICIPANTS: Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. METHODS: Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). MAIN OUTCOME MEASURES: Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. RESULTS: Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. CONCLUSIONS: The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study.

OBJECTIVE: To evaluate the 2-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema (DME). DESIGN: Twenty-four-month, open-label, multicenter, Phase IIIb extension study. PARTICIPANTS: Two hundred forty of 303 patients with visual impairment due to DME who completed the RESTORE core study and entered the extension. METHODS: All patients were eligible to receive ranibizumab 0.5 mg pro re nata (PRN) from month 12 (end of core study) to month 36 based on best-corrected visual acuity (BCVA) stability and disease progression retreatment criteria. Patients were also eligible to receive laser PRN according to Early Treatment Diabetic Retinopathy Study guidelines. A preplanned interim analysis was performed at month 24, stratifying by treatment groups as in the RESTORE core study and referred to as prior ranibizumab, ranibizumab plus laser, or laser groups in the extension. MAIN OUTCOME MEASURES: Incidence of ocular and nonocular adverse events (AEs) and mean change in BCVA. RESULTS: Two hundred twenty patients (92%) completed the month 24 visit. Over 2 years, the most frequent ocular serious AE (SAE) and AE were cataract (2.1%) and eye pain (14.6%), respectively. The main nonocular AEs were nasopharyngitis (18.8%) and hypertension (10.4%). There were no cases of endophthalmitis, and the incidences of nonocular SAEs were low. Of the patients entering the extension, 4 deaths were reported in the second year, none of which were related to study drug or procedure. Mean BCVA gain, central retinal thickness (CRT) decrease, and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) composite score observed at month 12 were maintained at month 24 (prior ranibizumab: +7.9 letters, -140.6 µm, and 5.6, respectively; prior ranibizumab plus laser: +6.7 letters, -133.0 µm, and 5.8, respectively), with an average of 3.9 (prior ranibizumab) and 3.5 ranibizumab injections (prior ranibizumab plus laser). In patients treated with laser alone in the core study, the mean BCVA, CRT, and NEI VFQ-25 composite score improved from month 12 to month 24 (+5.4 letters, -126.6 µm, and 4.3, respectively), with an average of 4.1 ranibizumab injections. CONCLUSIONS: Ranibizumab 0.5 mg administered according to prespecified visual stability and disease progression criteria was well tolerated, with no new safety concerns identified over 2 years. Overall, an average of 3.8 ranibizumab injections was sufficient to maintain (prior ranibizumab) or improve (prior laser) BCVA, CRT, and NEI VFQ-25 outcomes through the second year. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Short-term effect of macular edema on the peripapillary retinal nerve fiber layer in patients with wet age-related macular degeneration and diabetic macular edema: A comparative study.

BACKGROUND: The combined presence of glaucoma and age-related macular degeneration (ARMD), or glaucoma and diabetes mellitus (DM), occur fairly frequently, especially in elderly patients. This study was intended to compare the effect of resolving macular edema due to DM and wet ARMD on peripapillary retinal nerve fiber layer (RNFL) thickness. METHODS: This cross-sectional study included 76 patients with macular edema secondary to DM (n = 40, 52.6%) or wet ARMD (n = 36, 47.4%). The control group was comprised of 34 age and sex-matched healthy subjects. All study participants underwent evaluation of central macular thickness (CMT) and the peripapillary RNFL using spectral domain-optical coherence tomography (SD-OCT). Data from eyes that received an anti-VEGF injection were obtained one month after the procedure and were compared with pre-injection data. RESULTS: The average initial thickness of the global peripapillary RNFL was 98.9 ± 16.7 (61-163) µm in the macular edema group and 92.0 ± 16.0 (84-115) µm in the control group (p = 0.045). The post-injection global peripapillary RNFL thickness was 97.3 ± 19.0 (61-163) µm in the macular edema group and 92.2 ± 18.0 (81-126) µm in the control group (p = 0.187). In the DM group, the changes in global RNFL thickness, as well as central and temporal quadrant thicknesses, were found to correlate significantly with the change in CMT (r = 0.356, p = 0.024; r = 0.545, p < 0.001, respectively). CONCLUSIONS: Macular edema in wet ARMD appeared not to affect RNFL thickness. Differences in the etiology of macular edema can have varied effects on peripapillary RNFL. It is recommended that peripapillary RNFL thickness be evaluated cautiously in DM patients receiving intravitreal anti-VEGF therapy.

The management of neovascular age-related macular degeneration: A systematic literature review of patient-reported outcomes, patient mental health and caregiver burden.

PURPOSE: The aim of this systematic literature review was to describe patient-reported outcomes, mental health and caregiver burden in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents in routine clinical practice. METHODS: Electronic searches were conducted in Embase and MEDLINE according to pre-defined criteria. RESULTS: Of 856 records identified, 63 met inclusion criteria. Depression or depressive symptoms were reported in up to 42% of patients with nAMD. Of 25/63 (40%) studies evaluating quality of life (QoL) and using various tools, eight studies reported composite National Eye Institute Visual Functioning Questionnaire scores following anti-VEGF treatment. Of these, seven reported a statistically significant improvement at the earliest time point measured (Month 3-12) and approximately 50% reported sustained QoL benefits at 12 months. In studies comparing the attributed or different regimens, the most important factor from the patient's perspective was the likelihood that a particular regimen would maintain vision. There was a preference towards treat and extend, which was associated with a perceived reduction in patient and caregiver burden, compared to fixed dosing. CONCLUSIONS: A coordinated holistic approach to patient care is key to optimizing patient well-being as well as visual outcomes. Further research regarding the patient-reported impact of nAMD management outside the trial setting (particularly international longitudinal studies) is warranted. Standardization of QoL studies would assist in establishing whether sustained QoL improvement, rather than prevention of QoL decline, should be a realistic expectation of treatment of nAMD in the longer term.

Expert recommendations for the management of diabetic macular edema with intravitreal dexamethasone implant: A Turkish Delphi study.

PURPOSE: To provide consensus on the clinical use of intravitreal dexamethasone (DEX) implant for the treatment of diabetic macular edema (DME) in Turkey. METHODS: A panel of 22 retina experts prepared 77 statements of recommendation, and 80 retinal specialists practicing in Turkey were chosen to vote either in support or against each one. A Delphi-based method was used through which the ophthalmologists were able to view all of the results anonymously after two rounds and modify their subsequent answers. The survey was conducted via a mini website, and statements without consensus were resent to the specialists with the latest vote results a week later. RESULTS: A total of 72 ophthalmologists answered the first and second round questions. After the first stage, consensus was achieved on 55 of the statements, leaving 22 without agreement. After the second stage, consensus was reached on 11 of the remaining statements. Strong consensus was achieved on statements regarding the etiopathogenesis of DME and the first-line indications and safety of the DEX implant procedure. The panel recommended the use of DEX implant for patients with an arterial thromboembolic event in the last three months and also agreed that pro re nata DEX implant treatment not only provides better outcomes for DME patients but also reduces the treatment burden for those who could not receive an adequate number of anti-vascular endothelial growth factor (VEGF) injections. CONCLUSION: This study provides clinical consensus and recommendations about the use of DEX implant in the clinical practice of DME management in Turkey.

Ranibizumab therapy for predominantly hemorrhagic neovascular age-related macular degeneration.

Objective: Predominantly hemorrhage represents one of the possible manifestations of choroidal neovascularisation (CNV) in eyes with age-related macular degeneration (AMD). The purpose of this study is to evaluate the effecte of ranibizumab treatment in patients with predominantly hemorrhagic CNV secondary to AMD. Methods: Twenty-five patients with predominantly hemorrhagic choroidal neovascularization due to AMD with at least three ranibizumab injections and followed up for at least 12 months were included in the study. The months of follow-up were recorded (baseline, 3rd, 6th, and 12th months). The change in central macular thickness (CMT) on optical coherence tomography, visual acuity (VA) in ETDRS letters, and lesion size on fundus fluorescein angiography were evaluated. Results: The mean age of the patients was 68.1±5.7 (range: 63-82) years, the mean follow-up was 19.9±14.5 (range: 12-67) months, and the mean number of injections was 4.0±1.4 (range: 3-15). The initial VA was 39.3±17.9 (range: 1-65) letters, CMT was 272.7±104 (range: 164-587) µm, and the initial lesion width was 11.4±10.5 (range: 1.3-45.7) mm2. The VA was 41.4±20.1 (range: 5-75) and 36.9±21.8 (range: 4-80) letters (p=0.150), CMT was 270.7±110 (range: 159-570) and 230.4±108 (range: 109-667) µm (p=0.009) and the lesion width was 10.9±11.5 (range: 1.1-39.7) and 10.4±11.6 (range: 1.2-44.3) mm2 at 6th and 12th month, respectively. No factor was found to be associated with final CMT. Conclusion: Although the final visual outcome is limited by the progression of the disease, hemorrhagic lesions treated with ranibizumab have stable anatomical outcome.