Biomarkers determining treatment interval of diabetic macular edema after initial resolution by anti-vascular endothelial growth factor.

PURPOSE: To identify predictive factors that help determine the interval of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection after the initial resolution of diabetic macular edema (DME). METHODS: This retrospective case-control study enrolled treatment-naïve DME patients who had achieved DME resolution after intravitreal anti-VEGF injections. Patients were classified into the recurrence and no-recurrence groups, depending on the development of recurrent DME after deferring intravitreal anti-VEGF injection. The demographics and clinical features, including optical coherence tomography findings, were compared between the two groups. RESULTS: We enrolled 105 eyes. Sixty eyes (57.1%) belonged to the no-recurrence group, and 45 (42.9%), belonged to the recurrence group. The severity of diabetic retinopathy at baseline was related to early DME recurrence (P = 0.009). At the treatment deferring point, the non-recurrence group had both thinner central subfield thickness (289.5 ± 27.2 µm vs. 307.0 ± 38.2 µm, P = 0.011) and thinner central retinal thickness (214.9 ± 41.4 µm vs. 231.8 ± 41.2 µm, P = 0.043) compared to the recurrence group. Intraretinal cyst was observed in 34 eyes (56.7%) in the no-recurrence group and 42 eyes (93.3%) in the recurrence group at the deferring point (P < 0.001). CONCLUSION: A low risk of early DME recurrence is anticipated in the eyes with foveal thinning and no intraretinal cyst when anti-VEGF injection is deferred. These predictive biomarkers can be useful for patient monitoring and determining treatment strategies for DME patients.

Macular hole with epiretinal proliferation: diagnostic value of en-face optical coherence tomography and clinical characteristics.

PURPOSE: To elucidate the clinical features and surgical outcomes of full-thickness macular hole (FTMH) with epiretinal proliferation (EP) diagnosed by both en-face and B-mode optical coherence tomography (OCT). METHOD: This retrospective cohort study classified idiopathic FTMHs into two groups, based on B-scan and en-face OCT imaging: FTMH with EP (EP group) and without EP (non-EP group). The preoperative features, as well as postoperative outcomes up to 12 months, were compared between the two groups. RESULT: Among 318 eyes of idiopathic FTMH that met the inclusion criteria, 59 eyes (18.6%) were in the EP group, and others were in the non-EP group. In 9 eyes (15.3%) out of the EP group, EP was not detected in the preoperative B-mode OCT but was identified through the en-face OCT. Baseline features showed a higher male proportion (47.5% vs. 27.8%, P = 0.005) and a lower incidence of vitreofoveal traction (P < 0.001) in the EP group than in the non-EP group. The EP group showed worse visual recovery than the non-EP group (- 0.23 vs. - 0.41 logarithm of the minimum angle of the resolution at 12 months, P = 0.001). CONCLUSION: The en-face OCT enhances diagnostic accuracy of EP in FTMH eyes, especially in the case with smaller extent of EP. Eyes with FTMH with EP showed a worse visual recovery than FTMH without EP.

RISK OF EXUDATION IN EYES WITH NONEXUDATIVE POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To investigate the characteristics and natural history of treatment-naive nonexudative polypoidal choroidal vasculopathy (PCV) and to determine biomarkers predicting exudative conversion. METHODS: Patients diagnosed with nonexudative PCV based on indocyanine green angiography and optical coherence tomography were included. Incidence of exudative conversion in nonexudative PCV patients and cumulative estimates for overall risk were assessed. Indocyanine green angiography and optical coherence tomography imaging-based features were analyzed to identify risk factors for exudative conversion. RESULTS: The study included 42 eyes of 40 patients with nonexudative PCV. The mean follow-up duration was 54.3 ± 35.5 months. Of the 42 eyes with nonexudative PCV, exudative conversion developed in 23 eyes (54.8%) after 42.2 ± 28.3 months (range, 8-103 months). Kaplan-Meier analysis showed that the exudation-free survival at 5 years after baseline was estimated to be 53.6%. Multivariate regression analysis showed that sequentially increased protrusion of retinal pigment epithelium in the polyp area was a significant risk factor for exudation in nonexudative PCV (odds ratio = 10.16; 95% CI 1.78-57.81; P = 0.01). CONCLUSION: Exudative conversion has been noted in nearly half of the nonexudative PCV cases in 5 years. The progressive protrusion of polypoidal lesions on optical coherence tomography examination may be a significant biomarker for predicting the near-term onset of exudation.

THE IMPACT OF EARLY SURGICAL INTERVENTION ON ANISEIKONIA IN PATIENTS WITH EPIRETINAL MEMBRANE: A Prospective Cohort Study.

PURPOSE: To investigate the efficacy of early surgical intervention in ameliorating aniseikonia among patients with epiretinal membrane. METHODS: This prospective cohort study enrolled patients who underwent surgery for epiretinal membrane. Patients were divided into early (symptom onset within 1 year) and late (symptom onset ≥1 year) treatment groups. Changes in aniseikonia, best-corrected visual acuity, and tangential retinal displacement were assessed and compared at 6 and 12 months postoperatively. RESULTS: Of the 56 patients, 30 (53.6%) belonged to the early treatment group and 26 (46.4%) to the late treatment group. The early treatment group demonstrated a significant reduction in aniseikonia score at 6- and 12-month follow-up visits (-1.10 ± 1.50 [P = 0.002] and -1.18 ± 1.79 [P = 0.003], respectively); however, no improvement was observed in the late treatment group (0.98 ± 4.62 [P = 0.310] and 1.52 ± 4.35 [P = 0.124], respectively). The early treatment group showed larger tangential retinal displacement at the 12-month postoperative follow-up visit. In addition, the amount of tangential retinal displacement was associated with postoperative changes in aniseikonia. CONCLUSION: Early surgical intervention is helpful in improving aniseikonia in patients with epiretinal membrane. The degree of recovery in inner retinal displacement was associated with the improvement of aniseikonia.

Impact of Age-Related Macular Degeneration and Related Visual Disability on the Risk of Depression: A Nationwide Cohort Study.

PURPOSE: To evaluate the prospective association of age-related macular degeneration (AMD) and related visual disability (VD) with the risk of depression. DESIGN: This nationwide population-based cohort study used authorized clinical data provided by the Korean National Health Insurance Service. PARTICIPANTS: A total of 3 599 589 individuals older than 50 years participated in the Korean National Health Screening Program in 2009. METHODS: Age-related macular degeneration diagnosis and the presence of accompanying VD were verified using diagnostic codes and disability registration data. Data on covariates, including age, sex, income level, residential area, systemic comorbidities, and behavioral factors, were collected from health screening results and claims data. Patients were followed up until December 2019, and incident cases of depression were identified using registered diagnostic codes. The prospective association of AMD and related VD with new-onset depression was investigated using the multivariable-adjusted Cox proportional hazard model. MAIN OUTCOME MEASURES: Hazard ratios and 95% confidence intervals (CIs) for depression development according to the presence of AMD and VD. RESULTS: During an average follow-up period of 8.52 years, 1 037 088 patients received new diagnoses of depression. Patients with previous diagnoses of AMD showed a greater risk of new-onset depression, with a hazard ratio of 1.15 (95% CI, 1.13-1.17) compared with the control group in the fully adjusted model. Patients with AMD and accompanying VD showed a further increased risk of depression, with a hazard ratio of 1.23 (95% CI, 1.16-1.30). CONCLUSIONS: Individuals with a diagnosis of AMD have a higher risk of depression developing in the future. The risk of depression is increased further in patients with AMD who demonstrate VD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

SPONTANEOUS REATTACHMENT OF RHEGMATOGENOUS RETINAL DETACHMENT: Observations of the Vitreoretinal Interface.

PURPOSE: To describe the clinical characteristics and posterior vitreous findings of spontaneous reattachment of rhegmatogenous retinal detachment (SRRRD). METHODS: Eighty-six eyes from 80 patients who were diagnosed with SRRRD (SRRRD group) and 92 eyes from 92 patients who had undergone successful scleral buckling for rhegmatogenous retinal detachment ( group for comparison) were included. Ultrawide field fundus imaging and spectral domain optical coherence tomography were performed to evaluate fundus characteristics and vitreoretinal interface. RESULTS: A significant difference was found in the proportion of complete posterior vitreous attachment between the SRRRD and rhegmatogenous retinal detachment groups (44.2% vs. 19.6%, P < 0.001). The incidence of atypical epiretinal tissue (AET) in the SRRRD group was 14% (12 of 86 eyes), whereas none of the eyes in the rhegmatogenous retinal detachment group exhibited AET. In SRRRD eyes with AET, the visual acuity was lower (logarithm of the minimum angle of resolution, 0.51 ± 0.57 vs. 0.14 ± 0.15, P < 0.001), the mean age was higher (years, 61.7 vs. 39.4, P < 0.001), and the SRRRD lesion extent was wider (clock hours, 5.67 vs. 3.70, P = 0.004) than in SRRRD eyes without AET. CONCLUSION: Compared with the rhegmatogenous retinal detachment group, the SRRRD group had a higher incidence of posterior vitreous attachment. Furthermore, AET was a significant comorbidity in the eyes with SRRRD, particularly in the elderly and the area of presumed reattachment over two quadrants and was related to worse functional outcomes.

The clinical and pathogenic significance of atypical epiretinal tissue in macular hole.

With the recent advent of high-resolution optical coherence tomography (OCT), atypical epiretinal tissue (AET), also known as epiretinal proliferation, has been frequently noted in various pathologies. AET presents as premacular tissue with homogenous medium reflectivity over the internal limiting membrane on OCT. Although AET is most frequently associated with a lamellar hole (LH), some cases of macular hole (MH) also accompany AET at the edge of the hole. MH with AET has been reported to have worse clinical and surgical outcomes than MH without AET. The imaging and histopathological findings of AET imply that the development of MH with AET may not have been driven by vitreofoveal traction. Instead, MH with AET might have evolved from LH with AET. This mini-review encompassed relevant studies on MH with AET published to date and explained the clinical, prognostic, and pathogenic significance of AET in MH in detail.

Long-term outcomes of polypoidal choroidal vasculopathy in comparison with typical exudative age-related macular degeneration.

PURPOSE: To compare long-term outcomes between typical exudative age-related macular degeneration (TexAMD) and polypoidal choroidal vasculopathy (PCV), and to investigate factors related to the outcomes. METHODS: This retrospective study included 319 eyes (164 with TexAMD and 155 with PCV) treated with anti-vascular endothelial growth factor and followed more than 5 years. The primary outcome was visual acuity (VA) change from baseline to final visit. Linear regression analyses were used to determine factors associated with final VA. RESULTS: Baseline logMAR VA was 0.7 ± 0.5 in the TexAMD group and 0.5 ± 0.4 in the PCV group (p < 0.001). After a mean follow-up of 9 years, final VA was also significantly worse in the TexAMD group than in the PCV group (0.9 ± 0.6 vs. 0.6 ± 0.5; p < 0.001). The PCV group showed longer maintenance of improved vision and later onset of significant visual decline than the TexAMD group. In multivariate analysis, loss to follow-up, worse baseline VA, macular atrophy, and subretinal fibrosis were significantly associated with poor final VA in both groups. CONCLUSION: PCV eyes showed relatively favorable long-term visual outcome than TexAMD eyes. The results of this study emphasized the importance of compliance with treatment, along with other well-known prognostic factors.

PARAFOVEAL INNER RETINAL THINNING AS THE BIOMARKER PREDICTING LESS RECURRENCE OF MACULAR EDEMA IN CENTRAL RETINAL VEIN OCCLUSION AFTER DISCONTINUING ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR.

PURPOSE: To identify the predictive factors for the recurrence of macular edema after the cessation of antivascular endothelial growth factor treatment in eyes with central retinal vein occlusion (CRVO). METHODS: This retrospective study included participants who had discontinued intravitreal bevacizumab injections for complete resolution of macular edema related to CRVO at 3 months after the last injection. Fifty-two eyes were enrolled in this study and classified into two groups based on the recurrence of macular edema within 1 year after the stopping point, when the decision to discontinue injections was made. Clinical characteristics and optical coherence tomographic parameters at baseline and at the stopping point were investigated. RESULTS: Multivariate logistic regression analysis demonstrated that, at baseline, old age was associated with a significantly higher risk of macular edema recurrence (odds ratio, 1.092; P = 0.022). At the stopping point, parafoveal inner retinal thickness (odds ratio: 1.043, P = 0.014) and the presence of ellipsoid zone disruption (odds ratio: 5.922, P = 0.032) were predictive factors for recurrence. The receiver operating characteristic curve showed that parafoveal inner retinal thinning of >7 µm compared with that in the fellow eye was significantly associated with decreased recurrence of macular edema. CONCLUSION: Parafoveal inner retinal thinning and intact ellipsoid zone after resolution of macular edema by antivascular endothelial growth factor treatment were predictive of a lower risk of recurrence of macular edema in CRVO. These intuitive biomarkers may help predict future disease courses and design optimal treatment strategies.

EN-FACE IMAGING OF ATYPICAL EPIRETINAL TISSUE IN LAMELLAR MACULAR HOLE.

PURPOSE: To elucidate the significance of en-face optical coherence tomography imaging of atypical epiretinal tissue (AET) in the lamellar macular hole (LMH). METHODS: This study involved 29 eyes of 29 patients who underwent surgical treatment for LMH with AET. Best-corrected visual acuity, metamorphopsia assessment (M-score), and optical coherence tomography were evaluated before and 6 months after surgery. The novel en-face optical coherence tomography parameters, such as the area of AET and hyperreflective fringe, were correlated with clinical factors before and after LMH surgery. RESULTS: Preoperatively, hyperreflective fringe was noted in 25 (86.2%) patients. The splitting of the inner retina, disruption of the ellipsoid zone, the extent of foveal cavitation, symptom duration, and change in best-corrected visual acuity were correlated with the area of AET (all P < 0.05). Multivariate regression analysis revealed that a larger area of AET was associated with longer symptom duration and less improvement in postoperative vision (all P < 0.05). CONCLUSION: The area of AET may represent the chronicity of LMH and is significantly associated with visual outcomes after LMH surgery. This novel en-face optical coherence tomography parameter can be used as a predictive factor for surgical outcomes in LMH with AET.