Effectiveness of Conventional Digital Fundus Photography-Based Teleretinal Screening for Diabetic Retinopathy and Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: This American Academy of Ophthalmology Ophthalmic Technology Assessment aims to assess the effectiveness of conventional teleretinal screening (TS) in detecting diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: A literature search of the PubMed database was conducted most recently in July 2023 to identify data published between 2006 and 2023 on any of the following elements related to TS effectiveness: (1) the accuracy of TS in detecting DR or DME compared with traditional ophthalmic screening with dilated fundus examination or 7-standard field Early Treatment Diabetic Retinopathy Study photography, (2) the impact of TS on DR screening compliance rates or other patient behaviors, and (3) cost-effectiveness and patient satisfaction of TS compared with traditional DR screening. Identified studies then were rated based on the Oxford Centre for Evidence-Based Medicine grading system. RESULTS: Eight level I studies, 14 level II studies, and 2 level III studies were identified in total. Although cross-study comparison is challenging because of differences in reference standards and grading methods, TS demonstrated acceptable sensitivity and good specificity in detecting DR; moderate to good agreement between TS and reference-standard DR grading was observed. Performance of TS was not as robust in detecting DME, although the number of studies evaluating DME specifically was limited. Two level I studies, 5 level II studies, and 1 level III study supported that TS had a positive impact on overall DR screening compliance, even increasing it by more than 2-fold in one study. Studies assessing cost-effectiveness and patient satisfaction were not graded formally, but they generally showed that TS was cost-effective and preferred by patients over traditional surveillance. CONCLUSIONS: Conventional TS is an effective approach to DR screening not only for its accuracy in detecting referable-level disease, but also for improving screening compliance in a cost-effective manner that may be preferred by patients. Further research is needed to elucidate the ideal approach of TS that may involve integration of artificial intelligence or other imaging technologies in the future. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Treatment of Noninfectious Uveitic Macular Edema with Periocular and Intraocular Corticosteroid Therapies: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the effectiveness and complications of periocular and intraocular corticosteroid therapies for noninfectious uveitic macular edema. METHODS: A literature search of the PubMed database was conducted last in December 2021 and a post-assessment search was conducted in March 2023. The searches were limited to articles published in English and no date restrictions were imposed. The combined searches yielded 739 citations; 53 articles were selected for inclusion because the studies (1) evaluated periocular corticosteroid injection, intraocular corticosteroid injection or implant, suprachoroidal corticosteroid injection, or a combination thereof for uveitic macular edema; (2) had outcomes that included visual acuity (VA) or macular edema assessed clinically or imaged by OCT or fluorescein angiography; and (3) included more than 20 patients. RESULTS: This assessment reviewed 23 articles that provided level I or level II evidence from 18 studies on the use of periocular, suprachoroidal, and intravitreal triamcinolone acetonide injections and intravitreal dexamethasone and fluocinolone acetonide implants or inserts in noninfectious uveitic macular edema. These reports consistently demonstrated that all investigated periocular and intraocular corticosteroid therapies improved VA, macular structure, or both. One comparative study showed that intravitreal triamcinolone acetonide injection and the dexamethasone intravitreal implant had effectiveness superior to that of periocular triamcinolone acetonide injection for these outcomes. As a group, the studies highlighted the potential for these therapies to elevate intraocular pressure and to accelerate cataract formation. CONCLUSIONS: The published literature provides high-quality evidence that periocular and intraocular corticosteroid therapies are effective and safe for the treatment of noninfectious uveitic macular edema. However, information on the relative effectiveness and complication rates across the different therapies is limited. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Artificial Intelligence, Digital Imaging, and Robotics Technologies for Surgical Vitreoretinal Diseases.

OBJECTIVE: To review recent technological advancement in imaging, surgical visualization, robotics technology, and the use of artificial intelligence in surgical vitreoretinal (VR) diseases. BACKGROUND: Technological advancements in imaging enhance both preoperative and intraoperative management of surgical VR diseases. Widefield imaging in fundal photography and OCT can improve assessment of peripheral retinal disorders such as retinal detachments, degeneration, and tumors. OCT angiography provides a rapid and noninvasive imaging of the retinal and choroidal vasculature. Surgical visualization has also improved with intraoperative OCT providing a detailed real-time assessment of retinal layers to guide surgical decisions. Heads-up display and head-mounted display utilize 3-dimensional technology to provide surgeons with enhanced visual guidance and improved ergonomics during surgery. Intraocular robotics technology allows for greater surgical precision and is shown to be useful in retinal vein cannulation and subretinal drug delivery. In addition, deep learning techniques leverage on diverse data including widefield retinal photography and OCT for better predictive accuracy in classification, segmentation, and prognostication of many surgical VR diseases. CONCLUSION: This review article summarized the latest updates in these areas and highlights the importance of continuous innovation and improvement in technology within the field. These advancements have the potential to reshape management of surgical VR diseases in the very near future and to ultimately improve patient care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Functional Vision in Patients With Biallelic USH2A Variants.

PURPOSE: To describe functional vision (FV) and investigate the relationship between FV, visual acuity (VA), and hill of vision (VTOT) at baseline in patients with biallelic USH2A variants. DESIGN: Multicenter, international, cross-sectional study. METHODS: In individuals with biallelic disease-causing variants in USH2A, clinical diagnosis of Usher syndrome type 2 (USH2) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) was based on history of hearing loss and audiology examinations. The VALVVFQ-48 was administered verbally to participants ≥18 years old. VA was measured in both eyes; VTOT was determined from static perimetry in the study eye (better VA). FV scores were calculated using Rasch analysis. RESULTS: Median age of 121 participants (76 with USH2, 45 with ARRP) was 41 years (range: 19-80); 54% were female. FV scores varied from -2.0 to 7.6 logits (median [interquartile range (IQR)]: 2.8 [1.5-3.8]). ARRP and USH2 participants had similar FV scores, both before [mean (95% CI): 2.8 (2.3-3.4) and 2.7 (2.3-3.2), respectively], and after [mean (95% CI): 2.5 (2.1-3.0) and 2.9 (2.6-3.3), respectively; P = .24] adjusting for age, VA, disease duration, and VTOT. VA and VTOT accounted for 29% and 26% of the variance in FV scores, respectively (P < .001 for each). Together, they accounted for 36% of variance observed. CONCLUSIONS: Biallelic USH2A variants were associated with a large range of FV, yet similar in ARRP and USH2, despite hearing loss in USH2. The modified VALVVFQ-48 we evaluated is not ideal for detecting the impact of USH2A-associated retinal degenerations on activities of daily living.

Optimizing Visual Outcomes in Patients With Neovascular Age-Related Macular Degeneration: the Potential Value of Sustained Anti-VEGF Therapy.

Neovascular age-related macular degeneration (nAMD) leads to irreversible central vision loss if untreated. Frequent administration of anti-vascular endothelial growth factor (anti-VEGF) injections inhibits disease activity with excellent functional and morphological benefits. However, these injections pose a heavy therapeutic burden, and treatment discontinuation is common. Although current anti-VEGF treatment paradigms, such as treat-and-extend, mitigate treatment burden while still leading to acceptable vision outcomes, they fail to sustain initial vision gains for many. Novel longer-acting anti-VEGF therapies may reduce the overall burden on nAMD patients. Gene therapy might offer a paradigm shift by providing continuous expression of anti-VEGF, potentially decreasing treatment requirements and improving long-term vision outcomes. [Ophthalmic Surg Lasers Imaging Retina 2023;54:654-659.].

PRIMARY CENTRAL NERVOUS SYSTEM AND VITREORETINAL LYMPHOMA MIMICKING VIRAL RETINITIS IN A YOUNG PATIENT.

BACKGROUND/PURPOSE: The purpose of this study was to report a young immunocompetent patient with primary central nervous system and vitreoretinal lymphoma initially presenting with peripheral retinitis. METHODS: This study is a case report. RESULTS: A 31-year-old woman presented with 20/60 vision in her left eye, vitreous haze, and peripheral retinal whitening. Intravitreal and oral antivirals were initiated for presumed acute retinal necrosis. Anterior chamber paracentesis was negative for viral nucleotide. Subretinal infiltrates developed, and vitreous biopsy was performed and interpreted as "negative except for rare yeast." Antifungal therapy was initiated. She developed multiple unilateral cranial neuropathies with multifocal areas of enhancement on neuroimaging. Lumbar puncture cytology was negative for neoplastic cells. After further worsening, aforementioned specimens were sent to a specialized ophthalmic pathology laboratory and the diagnosis revised to lymphoma of the diffuse B-cell type. Initial disease regression was seen after combined systemic and intraocular chemotherapy; unfortunately, the patient suffered a central nervous system recurrence and died from systemic complications 1 year later. CONCLUSION: There has been an increased incidence of primary central nervous system and vitreoretinal lymphoma in young patients. Although vitreous biopsy is the diagnostic gold standard for vitreoretinal lymphoma, a risk of false negative interpretation exists. A high index of suspicion and expert interpretation of pathology may be necessary to secure the correct diagnosis.

Secretogranin III Selectively Promotes Vascular Leakage in the Deep Vascular Plexus of Diabetic Retinopathy.

Diabetic retinopathy (DR), a leading cause of vision loss in working-age adults, induces mosaic patterns of vasculopathy that may be associated with spatial heterogeneity of intraretinal endothelial cells. We recently reported that secretogranin III (Scg3), a neuron-derived angiogenic and vascular leakage factor, selectively binds retinal vessels of diabetic but not healthy mice. Here, we investigated endothelial heterogeneity of three retinal vascular plexuses in DR pathogenesis and the therapeutic implications. Our unique in vivo ligand binding assay detected a 22.7-fold increase in Scg3 binding to retinal vessels of diabetic mice relative to healthy mice. Functional immunohistochemistry revealed that Scg3 predominantly binds to the DR-stressed CD31- deep retinal vascular plexus but not to the relatively healthy CD31+ superficial and intermediate plexuses within the same diabetic retina. In contrast, VEGF bound to healthy and diabetic retinal vessels indiscriminately with low activity. FITC-dextran assays indicated that selectively increased retinal vascular leakage coincides with Scg3 binding in diabetic mice that was independent of VEGF, whereas VEGF-induced leakage did not distinguish between diabetic and healthy mice. Dose-response curves showed that the anti-Scg3 humanized antibody (hAb) and anti-VEGF aflibercept alleviated DR leakage with equivalent efficacies, and that the combination acted synergistically. These findings suggest: (i) the deep plexus is highly sensitive to DR; (ii) Scg3 binding to the DR deep plexus coincides with the loss of CD31 and compromised endothelial junctions; (iii) anti-Scg3 hAb alleviates vascular leakage by selectively targeting the DR-stressed deep plexus within the same diabetic retina; (iv) combined anti-Scg3 and anti-VEGF treatments synergistically ameliorate DR through distinct mechanisms.

Safety of recent ophthalmic drugs and devices for wet macular degeneration.

PURPOSE OF REVIEW: With frequent antivascular endothelial growth factors (VEGF) injections well established as the standard of care in neovascular age-related macular degeneration (nAMD), focus has now shifted towards decreasing treatment burden without compromising safety and efficacy. This review summarizes clinical stage and recently approved drugs and devices for nAMD, with an emphasis paid to safety concerns and their implications for product adoption. RECENT FINDINGS: Three strategies have emerged to decrease the treatment burden associated with the current standard of care: more durable intravitreal agents, sustained-release modalities and gene therapy. The appearance of biosimilars will further impact drug availability and cost. As patterns of adverse events emerge from clinical trial or postmarketing surveillance data, manufacturers have proactively responded by appointing independent review committees or issuing voluntary recalls. However, the example of one biosimilar approved outside of the USA and European Union demonstrates how early safety concerns, even when addressed by substantive data, can generate lingering uncertainty. SUMMARY: As the number of promising new treatments in nAMD continues to grow, so too does the amount of data that providers must sift through. The perception of safety surrounding first movers in each new therapeutic area is sure to affect adoption of that modality more broadly.

Multimodal Imaging of Choroidal Lesions in an Elderly Man With Uveal Lymphoid Hyperplasia.

Purpose: To describe the case of an elderly man who was incidentally found to have multiple hypopigmented choroidal lesions in the left eye in the absence of intraocular inflammation. Methods: A case report was analyzed, including the laboratory workup and imaging results. Results: The workup for conditions, including birdshot chorioretinopathy, syphilis, and tuberculosis, were negative. Ancillary imaging confirmed a diagnosis of uveal lymphoid hyperplasia (ULH). The patient was stable under observation for more than 1 year. Conclusions: Careful examination and imaging findings can aid in differentiating between ULH and other diagnoses.

Epidemiology of Retinopathy of Prematurity in the US From 2003 to 2019.

Importance: Retinopathy of prematurity (ROP) is a potentially blinding retinal disease with poorly defined epidemiology. Understanding of which infants are most at risk for developing ROP may foster targeted detection and prevention efforts. Objective: To identify changes in ROP incidence in the US from 2003 to 2019. Design, Setting, and Participants: This retrospective database cohort study used the Healthcare Cost and Utilization Project Kids' Inpatient Databases. These nationwide databases are produced every 3 years, include data from over 4000 hospitals, and are designed to generate national estimates of health care trends in the US. Participants included pediatric newborns at risk for ROP development between 2003 and 2019. Data were analyzed from September 30, 2021, to January 13, 2022. Exposures: Premature or low-birth-weight infants with relevant International Classification of Diseases, Ninth Revision or Tenth Revision codes were considered ROP candidates. Infants with ROP were identified using relevant codes. Main Outcomes and Measures: ROP incidence in selected subpopulations (based on database-reported race and ethnicity, sex, location, income) was measured. To determine whether incidences varied across time or subpopulations, χ2 tests of independence were used. Results: This study included 125 212 ROP discharges (64 715 male infants [51.7%]) from 23 187 683 births. The proportion of premature infants diagnosed with ROP increased from 4.4% (11 720 of 265 650) in 2003 to 8.1% (27 160 of 336 117) in 2019. Premature infants from the lowest median household income quartile had the greatest proportional increase of ROP diagnoses from 4.9% (3244 of 66 871) to 9.0% (9386 of 104 235; P < .001). Premature Black infants experienced the largest increase from 5.8% (2124 of 36 476) to 11.6% (7430 of 63 925; P < .001) relative to other groups (2.71%; 95% CI, 2.56%-2.87%; P < .001). Hispanic infants experienced the second largest increase from 4.6% (1796 of 39 106) to 8.2% (4675 of 57 298; P < .001) relative to other groups (-0.16%; 95% CI, -0.29% to -0.03%; P = .02). The Southern US experienced the greatest proportional growth of ROP diagnoses, increasing from 3.7% (3930 of 106 772) to 8.3% (11 952 of 144 013; P < .001) relative to other groups (1.61%; 95% CI, 1.51%-1.71%; P < .001). ROP diagnoses proportionally increased in urban areas and decreased in rural areas. Conclusions and Relevance: This cohort study found that ROP incidence among premature infants increased from 2003 to 2019, especially among Black and Hispanic infants. Infants from the lowest-income areas persistently had the highest proportional incidence of ROP, and all regions experienced a significant increase in ROP incidence with the most drastic changes occurring in the South. These trends suggest that ROP is a growing problem in the US and may be disproportionately affecting historically marginalized groups.