LONG-TERM USE OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Although pivotal trials have demonstrated efficacy of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration, there is a paucity of clinical data about the long-term (>5 years) treatment. METHODS: Retrospective analysis of all patients with neovascular age-related macular degeneration who were actively treated, had received >40 anti-vascular endothelial growth factor injections, and were followed for ≥5 years. Snellen-corrected visual acuity, initial drug choice, and times elapsed between treatments were collected. Rates of endophthalmitis and outcomes of submacular hemorrhage were also evaluated. RESULTS: A total of 88 patients (162 eyes) met the inclusion criteria: the average patient age was 86.3 years with an average follow-up period of 7.6 years. The average total number of injections per eye was 69 (18.0 SD); a total of 11,208 injections were given throughout the study period, and 6 cases (0.05%) of endophthalmitis were observed. Overall, there was a clinical and statistical difference in average Snellen-corrected visual acuity at Injections #2,#3, #4, #5, #6, #10, and #20, as compared with baseline ( P = 0.03, P < 0.01, P = 0.02, P < 0.01, P = 0.01, P = 0.01, P < 0.01, respectively). Patients in the Snellen-corrected visual acuity subgroup 20/20 to 20/40 maintained vision until injection #30. Seven eyes experienced a visually significant submacular hemorrhage. CONCLUSION: This neovascular age-related macular degeneration cohort received on average eight anti-vascular endothelial growth factor injections per year for approximately 8 years; eyes with good (≥20/40) initial baseline vision maintained their visual acuity, whereas those with worse Snellen-corrected visual acuity (≤20/50) had a robust initial improvement that diminished with time. Most patients were maintained on the same initial drug of choice and the rate of endophthalmitis was low.

The Incidence and Timing of Treatment-Requiring Retinopathy of Prematurity in Nanopremature and Micropremature Infants in the United States: A National Multicenter Retrospective Cohort Study.

PARTICIPANTS: This article includes 7293 infants (14 586 eyes) screened for ROP across 5 centers in the United States (Austin Retina Associates, Austin, TX; Bascom Palmer Eye Institute, Miami, FL; Beaumont Eye Institute, Royal Oak, MI; Massachusetts Eye and Ear, Boston, MA; and Stanford Byers Eye Institute, Stanford, CA). PURPOSE: To analyze the incidence and timing of treatment requiring retinopathy of prematurity (ROP) in extremely small premature infants. We hypothesize that the smaller the infant by gestational age and birthweight, the higher their likelihood of requiring treatment for ROP. DESIGN: Premature infants screened for Retinopathy of Prematurity from 2002-2022 were divided into cohorts based on the following criteria based on gestational age (GA) and birth weight (BW). "Micropremature infants" are infants born between 24-26 weeks GA and between 600-799 g BW. "Nanopremature infants" are born ≤ 24 weeks GA and ≤ 600 g BW. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: The incidence and timing of treatment-requiring ROP. RESULTS: We found that infants defined as nanopremature had a ∼63% chance of requiring treatment at an average postmenstrual age (PMA) of 36.6 weeks, whereas those defined as micropremature had a 30% chance of requiring treatment at an average PMA of 36.3 weeks. This significantly contrasts with the risk of all screened babies for ROP where the risk of requiring treatment was 8.5%. CONCLUSION: Micropremature and nanopremature infants are significantly more likely to require treatment for ROP. With demographic data matched to all 5 major US regions spanning the last decade, these results have the potential to inform neonatologists, pediatricians, and ophthalmologists of an important shift in the landscape of prematurity in the United States. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Literary Pediatric Retina Fellowship With Michael T. Trese, MD.

Michael T. Trese, MD (1946-2022), a vitreoretinal surgeon, made significant contributions to the field of retina. Although most known for his work in pediatric retina surgery, he was a pioneer in areas such as medical retina, translational research, and telemedicine. This article reviews his major contributions to spread his knowledge more widely to vitreoretinal trainees and specialists. We discuss six areas where Trese made a lasting impact: lens-sparing vitrectomy, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, autologous plasmin enzyme, regenerative medicine, and telemedicine. [Ophthalmic Surg Lasers Imaging Retina 2023;54:701-712.].

Mechanisms Underlying Rare Inherited Pediatric Retinal Vascular Diseases: FEVR, Norrie Disease, Persistent Fetal Vascular Syndrome.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function, and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway, such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goal of this review is to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Retinal detachment in a pediatric patient with enhanced S-cone syndrome.

Enhanced S-cone syndrome (ESCS), also known as Goldmann-Favre syndrome, is a retinal degeneration that presents in childhood and leads to progressive nyctalopia and visual field loss. In advanced cases, this degeneration can result in loss of central visual acuity. We describe the case of a 15-year-old boy with ESCS who presented with retinal detachment, a rare complication.

Variability in Plus Disease Diagnosis using Single and Serial Images.

PURPOSE: To assess changes in retinopathy of prematurity (ROP) diagnosis in single and serial retinal images. DESIGN: Cohort study. PARTICIPANTS: Cases of ROP recruited from the Imaging and Informatics in Retinopathy of Prematurity (i-ROP) consortium evaluated by 7 graders. METHODS: Seven ophthalmologists reviewed both single and 3 consecutive serial retinal images from 15 cases with ROP, and severity was assigned as plus, preplus, or none. Imaging data were acquired during routine ROP screening from 2011 to 2015, and a reference standard diagnosis was established for each image. A secondary analysis was performed using the i-ROP deep learning system to assign a vascular severity score (VSS) to each image, ranging from 1 to 9, with 9 being the most severe disease. This score has been previously demonstrated to correlate with the International Classification of ROP. Mean plus disease severity was calculated by averaging 14 labels per image in serial and single images to decrease noise. MAIN OUTCOME MEASURES: Grading severity of ROP as defined by plus, preplus, or no ROP. RESULTS: Assessment of serial retinal images changed the grading severity for > 50% of the graders, although there was wide variability. Cohen's kappa ranged from 0.29 to 1.0, which showed a wide range of agreement from slight to perfect by each grader. Changes in the grading of serial retinal images were noted more commonly in cases of preplus disease. The mean severity in cases with a diagnosis of plus disease and no disease did not change between single and serial images. The ROP VSS demonstrated good correlation with the range of expert classifications of plus disease and overall agreement with the mode class (P = 0.001). The VSS correlated with mean plus disease severity by expert diagnosis (correlation coefficient, 0.89). The more aggressive graders tended to be influenced by serial images to increase the severity of their grading. The VSS also demonstrated agreement with disease progression across serial images, which progressed to preplus and plus disease. CONCLUSIONS: Clinicians demonstrated variability in ROP diagnosis when presented with both single and serial images. The use of deep learning as a quantitative assessment of plus disease has the potential to standardize ROP diagnosis and treatment.

A Survey of Multigenic Protein-Altering Variant Frequency in Familial Exudative Vitreo-Retinopathy (FEVR) Patients by Targeted Sequencing of Seven FEVR-Linked Genes.

While Inherited Retinal Diseases (IRDs) are typically considered rare diseases, Familial Exudative Vitreo-Retinopathy (FEVR) and Norrie Disease (ND) are more rare than retinitis pigmentosa. We wanted to determine if multigenic protein-altering variants are common in FEVR subjects within a set of FEVR-related genes. The potential occurrence of protein-altering variants in two different genes has been documented in a very small percentage of patients, but potential multigenic contributions to FEVR remain unclear. Genes involved in these orphan pediatric retinal diseases are not universally included in available IRD targeted-sequencing panels, and cost is also a factor limiting multigenic-sequence-based testing for these rare conditions. To provide an accurate solution at lower cost, we developed a targeted-sequencing protocol that includes seven genes involved in Familial Exudative Vitreo-Retinopathy (FEVR) and Norrie disease. Seventy-six DNA samples from persons refered to clinic with possible FEVR and some close relatives were sequenced using a novel Oakland-ERI orphan pediatric retinal disease panel (version 2) providing 900 times average read coverage. The seven genes involved in FEVR/ND were: NDP (ChrX), CTNNB1 (Chr3); TSPAN12 (Chr7); KIF11 (Chr10), FZD4 (Chr11), LRP5 (Chr11), ZNF408 (Chr11). A total of 33 variants were found that alter protein sequence, with the following relative distribution: LRP5 13/33 (40%), FZD4 9/33 (27%), ZNF408 6/33 (18%), (KIF11 3/33 (9%), NDP 1/33 (3%), CTNNB1 1/33 (3%). Most protein-altering variants, 85%, were found in three genes: FZD4, LRP5, and ZNF408. Four previously known pathogenic variants were detected in five families and two unrelated individuals. Two novel, likely pathogenic variants were detected in one family (FZD4: Cys450ter), and a likely pathogenic frame shift termination variant was detected in one unrelated individual (LRP5: Ala919CysfsTer67). The average number of genes with protein-altering variants was greater in subjects with confirmed FEVR (1.46, n = 30) compared to subjects confirmed unaffected by FEVR (0.95, n = 20), (p = 0.009). Thirty-four percent of persons sequenced had digenic and trigenic protein-altering variants within this set of FEVR genes, which was much greater than expected in the general population (3.6%), as derived from GnomAD data. While the potential contributions to FEVR are not known for most of the variants in a multigenic context, the high multigenic frequency suggests that potential multigenic contributions to FEVR severity warrant future investigation. The targeted-sequencing format developed will support such exploration by reducing the testing cost to $250 (US) for seven genes and facilitating greater access to genetic testing for families with this very rare inherited retinal disease.

Capillary density and caliber as assessed by optical coherence tomography angiography may be significant predictors of diabetic retinopathy severity.

PURPOSE: To validate retinal capillary density and caliber associations with diabetic retinopathy (DR) severity in different clinical settings. METHODS: This cross-sectional study assessed retinal capillary density and caliber in the superficial retinal layer of 3-mm OCTA scans centered on the fovea. Images were collected from non-diabetic controls and subjects with mild or referable DR (defined DR worse than mild DR) between February 2016 and December 2019 at secondary and tertiary eye care centers. Vessel Skeleton Density (VSD), a measure of capillary density, and Vessel Diameter Index (VDI), a measure of vascular caliber, were calculated from these images. Discriminatory performance of VSD and VDI was evaluated using multivariable logistic regression models predicting DR severity with adjustments for sex, hypertension, and hyperlipidemia. Area under the curve (AUC) was estimated. Model performance was evaluated in two different cohorts. RESULTS: This study included 594 eyes from 385 subjects. Cohort 1 was a training cohort of 509 eyes including 159 control, 155 mild non-proliferative DR (NPDR) and 195 referable DR eyes. Cohort 2 was a validation cohort consisting of 85 eyes including 16 mild NPDR and 69 referable DR eyes. In Cohort 1, addition of VSD and VDI to a model using only demographic data significantly improved the model's AUC for discrimination of eyes with any DR severity from controls (0.91 [95% CI, 0.88-0.93] versus 0.80 [95% CI, 0.76-0.83], p < 0.001) and eyes with referable DR from mild NPDR (0.90 [95% CI, 0.86-0.93] versus 0.69 [95% CI, 0.64-0.75], p < 0.001). The transportability of this regression model was excellent when implemented in Cohort 2 for the referable DR versus mild NPDR comparison. The odds ratio of having any DR compared to control subjects, and referable DR compared to mild DR decreased by 15% (95% CI: 12-18%), and 13% (95% CI: 10-15%), respectively, for every 0.001 unit increase in VSD after adjusting for comorbidities. CONCLUSION: OCTA-derived capillary density has real world clinical value for rapidly assessing DR severity.

Referable Macular Hemorrhage-A Clinically Meaningful Screening Target in Newborn Infants. Position Statement of the Association of Pediatric Retina Surgeons.

Universal newborn eye screening facilitates early diagnosis of ocular abnormalities and mitigates vision loss. "Referral warranted" eye disease is present at birth in about 5.5% of term infants, with "macular hemorrhage impinging on the fovea" representing about 50% of referral warranted disease. The Association of Pediatric Retina Surgeons held a symposium on February 9, 2021 that culminated in a position statement on "referable macular hemorrhage" (RMH) in newborn infants. RMH is meaningful in that in can cause amblyopia through deprivation, can be readily captured with wide-angle photography in a safe and efficient manner, and may lead to early intervention with mitigation of vision loss. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:3-6.].

LONG-TERM VISUAL OUTCOMES AND THE TIMING OF SURGICAL REPAIR OF FOVEA-SPLITTING RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: To evaluate the visual outcomes and the affect of timing of surgical repair of fovea-splitting rhegmatogenous retinal detachments. METHOD: A retrospective, consecutive cohort from multiple surgeons at a single center. Fovea status (fovea-on, fovea-splitting, or fovea-off) was classified by preoperative optical coherence tomography. The primary outcome measure was the visual acuity at the last follow-up that was further correlated with the timing of surgical repair. RESULTS: One hundred and ninety-five eyes were included with 62 fovea-on, 65 fovea-splitting, and 68 fovea-off detachments. The mean preoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups was 0.16 ± 0.21, 0.70 ± 0.56, and 1.67 ± 0.87, respectively (P = <0.001). Mean postoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups were 0.07 ± 0.13, 0.10 ± 0.15, and 0.20 ± 0.22, respectively (P = <0.001). A statistically significant difference in mean postoperative logMAR visual acuity was found between fovea-off and fovea-on groups (P = 0.003) and between fovea-off and fovea-splitting groups (P = 0.013), however not between fovea-on and fovea-splitting groups (P = 0.827). Visual acuity improved when repair was performed earlier after presentation for fovea-on (R = 0.378, P = 0.002) and fovea-off groups (R = 0.277, P = 0.022), but not for the fovea-splitting group (R = 0.089, P = 0.481). CONCLUSION: We described the favorable visual outcomes of surgery for fovea-splitting rhegmatogenous retinal detachment and correlated these with the timing of surgical repair, which may help guide the management of this urgent, vision-threatening condition.

Management of Type 2 Retinopathy of Prematurity or Less in Infants Aged 45 Weeks Postmenstrual Age or Older.

BACKGROUND AND OBJECTIVE: This study aimed to identify the degree of concordance between fluorescein angiograms (FA) and fundus photographs (FP) in assessing the severity and potential need for treatment in infants 45 weeks or older postmenstrual age (PMA) with type 2 or less retinopathy of prematurity (ROP). PATIENTS AND METHODS: An observational retrospective case series performed at Associated Retinal Consultants, William Beaumont Hospital in Royal Oak, Michigan. All infants born between 2006 and 2016 with stage 1 to 3 ROP that did not meet type 1 ROP criteria (type 2 or less) who received ablative laser therapy during or after age 45 weeks PMA. Pretreatment FP and FA images were randomized and sent to nine expert retina specialist graders to assess severity and inter-grader variability. RESULTS: A total of 10 babies (19 eyes) were enrolled in this study, and 53 FAs and 27 FPs of these 19 eyes were selected to be interpreted by the nine graders. The number of eyes deemed to be abnormal and warranted for treatment was higher with FA, whereas more eyes were deemed "normal" with FP. CONCLUSION: Although still controversial, knowledge of these findings may encourage retina specialists to closely examine infants with mild ROP older than age 45 weeks PMA and consider ablative laser therapy under certain conditions (even if not meeting type 1 Early Treatment for ROP criteria). [Ophthalmic Surg Lasers Imaging Retina. 2021;52:636-641.].

Retrospective Study of Ellipsoid Zone Integrity Following Treatment with Intravitreal Ocriplasmin (OZONE Study).

PURPOSE: To assess generalized (GD) and focal ellipsoid zone disruption (FD) in patients with symptomatic vitreomacular adhesion (sVMA) using spectral domain optical coherence tomography (SD-OCT) following ocriplasmin. PATIENTS AND METHODS: OZONE was a Phase 4, retrospective study of patients with sVMA treated with a single intravitreal injection of ocriplasmin (0.125 mg). Data from adult patients with at least 6-month follow-up after ocriplasmin were included. SD-OCT was performed at baseline (within 30 days before ocriplasmin), before Day 21 post-injection (early observation, EO), and by last observation (LO) which was maximally 6 months post-injection. The main outcome measure was the development of new and the evolution of existing FD/GD at EO and LO. RESULTS: The study enrolled 134 eyes/patients from 22 sites in the USA. At baseline, 87 eyes (64.9%) had FD, 21 eyes (15.7%) had GD and 26 eyes (19.4%) had no FD/GD. Among the eyes without FD/GD at baseline, 13 (50%) and 8 (30.8%) developed FD or GD, respectively, by EO. By LO, FD/GD improvement or resolution was seen in >80% of these eyes. Among the eyes with FD/GD at baseline, <40% had improving/resolving EZ integrity at LO. The absence of FD/GD at baseline was associated with less persistent FD/GD at LO (P<0.0005). The presence of FD with MH at baseline was associated with persistent FD at LO (P=0.027). CONCLUSION: The fact that a large majority of eyes had FD/GD prior to ocriplasmin was unexpected and demonstrates that EZ disruptions are common in sVMA. This suggests that loss of EZ integrity may be part of the natural history of this disorder. It is hypothesized that the status of the EZ at baseline is a contributing, ocriplasmin independent modulator of subsequent EZ changes after ocriplasmin. Prospective analyses which include a sham control group would be required to test this hypothesis.

Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes.

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease affecting premature infants. In addition to prematurity itself and oxygen treatment, genetic factors have been suggested to predispose to ROP. We aimed to identify potentially pathogenic genes and biological pathways associated with ROP by analyzing variants from whole exome sequencing (WES) data of premature infants. As part of a multicenter ROP cohort study, 100 non-Hispanic Caucasian preterm infants enriched in phenotypic extremes were subjected to WES. Gene-based testing was done on coding nonsynonymous variants. Genes showing enrichment of qualifying variants in severe ROP compared to mild or no ROP from gene-based tests with adjustment for gestational age and birth weight were selected for gene set enrichment analysis (GSEA). Mean BW of included infants with pre-plus, type-1 or type 2 ROP including aggressive posterior ROP (n = 58) and mild or no ROP (n = 42) were 744 g and 995 g, respectively. No single genes reached genome-wide significance that could account for a severe phenotype. GSEA identified two significantly associated pathways (smooth endoplasmic reticulum and vitamin C metabolism) after correction for multiple tests. WES of premature infants revealed potential pathways that may be important in the pathogenesis of ROP and in further genetic studies.

Interest in Telehealth Among Patients With Chronic Retinal Conditions.

Purpose: This work investigated interest in telehealth services for patients with chronic retinal conditions. Methods: A single-center, multi-office study was conducted of patients with chronic retinal conditions who were seen by 1 of 4 physicians during June 2020. Patients whose next appointment was 6 months or later were telephoned. Patients completed a phone interest survey about their interest in a hybrid telehealth evaluation instead of a complete office evaluation with their provider. Results: Of 2136 patients reviewed, 453 met eligibility to participate in the survey. A total of 159 patients (35.1%) participated, of whom 91 (57.2%) indicated an interest in telehealth at their next follow-up visit. Of the 68 (42.8%) patients without a current interest in telehealth, 13 (19.1%) expressed interest in pursuing telehealth in the future. Age (P = .19), sex (P = .22), race (P = .79), office location (P = .19), number of prior visits (P = .58), and median household income by patient's zip code (P = .14) were not predictors of telehealth interest. Among diagnoses, dry age-related macular degeneration was associated (P = .04) with increased interest in telehealth. An increased number of ocular diagnoses were also found to predict a decreased (P = .04) interest in telehealth. multivariable analysis revealed healthcare provider as the only significant predictor for interest in telehealth (P = .03). Conclusions: Most patients with chronic retinal conditions may be interested in incorporating telehealth into routine care. Considerations should be made to evaluate interest in telehealth to guide patients to clinical experiences that best suit their needs.

PERIPHERAL RETINAL ANGIOGRAPHIC FINDINGS IN MACULAR TELANGIECTASIS TYPE 2.

PURPOSE: To evaluate the retinal periphery in patients with idiopathic juxtafoveal telangiectasis or macular telangiectasis Type 2 (MacTel2), using widefield fluorescein angiography. METHODS: Single-center, retrospective, observational case series of 50 eyes of 50 patients with MacTel2 and 50 eyes of 50 age-matched controls. RESULTS: Thirty-seven eyes in the MacTel2 group (74%) showed peripheral capillary nonperfusion or dropout, compared with 37 eyes in the control group (74%, P = 1.0). Morphologically, the MacTel2 group trended toward having a higher proportion of pruning-type capillary dropout (44%) compared with controls (28%), but this was not statistically significant (P = 0.12). Patients with MacTel2 had a higher incidence of microaneurysms compared with controls (MacTel2 56%; controls 42%; P = 0.048), independent of age or systemic risk factors. There was no difference in the incidence of venous-venous shunts (MacTel2 10%; controls 10%; P = 1.0), arteriovenous shunts (MacTel2 14%; controls 18%; P = 0.60), venous tortuosity (MacTel2 60%; controls 66%; P = 0.58), or arterial tortuosity (MacTel2 54%; controls 68%; P = 0.20), which was mild in most cases. CONCLUSION: We note a high incidence of peripheral vascular and retinal findings in both patients with MacTel2 and age-matched controls, using widefield fluorescein angiography. Patients with MacTel2 had significantly more microaneurysms, independent of age or other systemic risk factors.

CLINICAL OUTCOMES AND TREATMENT COURSE OF EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FOLLOWING THE DEVELOPMENT OF ENDOPHTHALMITIS.

PURPOSE: To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections. METHODS: Multicenter, retrospective series. RESULTS: From April 2013 to October 2018, 196,598 intravitreal anti-vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P < 0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P < 0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P < 0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumab > bevacizumab; P < 0.001). CONCLUSION: Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.

The retina revolution: signaling pathway therapies, genetic therapies, mitochondrial therapies, artificial intelligence.

PURPOSE OF REVIEW: The aim of this article is to review and discuss the history, current state, and future implications of promising biomedical offerings in the field of retina. RECENT FINDINGS: The technologies discussed are some of the more recent promising biomedical developments within the field of retina. There is a US Food and Drug Administration-approved gene therapy product and artificial intelligence device for retina, with many other offerings in the pipeline. SUMMARY: Signaling pathway therapies, genetic therapies, mitochondrial therapies, and artificial intelligence have shaped retina care as we know it and are poised to further impact the future of retina care. Retina specialists have the privilege and responsibility of shaping this future for the visual health of current and future generations.

The Presence of Wnt Signaling Mutations in Patients With Diabetic Retinopathy.

Purpose: The relationship between poor hemoglobin A1c (HbA1c) control and risk of proliferative diabetic retinopathy (PDR) is well known. Nevertheless, some patients have discordant disease (controlled HbA1c and severe PDR or vice versa). One potential explanation for this discrepancy is the presence of underlying genetic mutations in the Wingless-related integration site (Wnt) signaling pathway. However, minimal clinical data exist on the presence of Wnt signaling mutations in patients with diabetes mellitus (DM) and the correlation with diabetic retinopathy. Methods: Retrospective, nonconsecutive case review of patients with type 1 or 2 DM who underwent genetic testing for at least 1 recognized Wnt signaling pathway mutation from 2011 to 2016. The clinical course and retinal images were reviewed for patients with identifiable mutations. Results: Thirty-six patients, ages 13 to 79 years, consented for genetic analysis. Three patients (8.3%) exhibited at least 1 recognized genetic mutation in the Wnt signaling pathway. Case 1 was a 65-year-old female with type 1 diabetes for > 20 years, HbA1c <7.0%, and no findings of diabetic retinopathy (Tetraspanin 12). Case 2 was a 13-year-old male with type 1 diabetes for 8 years, moderate HbA1c control (7.6-8.3%), and absence of diabetic retinopathy (Norrin). Case 3 was a 48-year-old male with severe PDR requiring multiple laser and antivascular endothelial growth factor (anti-VEGF) treatments despite well-controlled HbA1c (6.0%) (Frizzled-4). Conclusion: Wnt signaling pathway mutations exist in patients with DM. Further studies investigating the prevalence and clinical significance of these mutations in a larger diabetic population are warranted. Identification of these patients with genetic testing may enable earlier medical intervention.