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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).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.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 of7 µm compared with that in the fellow eye was significantly associated with decreased recurrence of macular edema.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.

AR-1105 is a novel biodegradable sustained-release dexamethasone implant designed to deliver 6-month durability. This Phase 2 study evaluated two AR-1105 formulations with different release profiles in patients with macular edema due to retinal vein occlusion.Patients received a single intravitreal injection with 340 µg dexamethasone. In the initial phase, five patients received clinical formulation (CF) 1. In the randomized phase, 44 patients were randomized 1:1 to CF1 or CF2. The follow-up was 6 months. Patients had vision loss due to macular edema diagnosed ≥9 (central retinal vein occlusion) or ≥12 months (branch retinal vein occlusion) before screening, and could be treatment-naive or -experienced (if received prior steroids, must have demonstrated response).Both formulations improved vision and reduced retinal thickening from baseline across all visits. At Month 6, mean changes in best-corrected visual acuity were +4.3 and +8.0 letters, and mean changes in central subfield thickness were -93 µm and -211 µm in CF1 and CF2 randomized patients, respectively. Most common adverse events were reduced visual acuity, worsening macular edema, conjunctival hemorrhage, and increased intraocular pressure. No patients required surgery or laser for intraocular pressure control.Both formulations were well tolerated and demonstrated clinically meaningful and sustained improvements in vision and retinal thickening in patients with retinal vein occlusion with longstanding edema.

To compare safety and therapeutic effect of three treatment protocols on patients with naive proliferative diabetic retinopathy.A total of 207 eyes with proliferative diabetic retinopathy were randomly divided into three groups: full panretinal photocoagulation group; intravitreal bevacizumab (IVB) group with four monthly IVB injections; and modified combination group with two bimonthly IVB injections and a modified laser therapy. The best-corrected visual acuity and area of neovascularization leakage were compared at 1-year follow-up.The difference in final best-corrected visual acuity was not significant between the groups (P = 0.77). The modified combination group had the lowest final leakage area (P = 0.006). The difference in final mean deviation of visual field was not significant between IVB and modified combination groups (mean difference = 0.25, P = 0.23, 95% confidence interval, 0.12-1.38). There was no difference in rate of new-onset diabetic macular edema between IVB and modified combination groups (mean difference = 1.5%, P = 0.31, 95% confidence interval, 1.1-1.88). Mean of total IVB injections were 3.5, 7.4, and 6.2 for panretinal photocoagulation, IVB, and modified combination groups, respectively (P = 0.002). Patients in the IVB group underwent more visits (P = 0.001). In subgroup analysis, the difference in the final leakage area was significant for the eyes with diabetic macular edema (P = 0.005).A combination protocol of photocoagulation and IVB can be recommended for proliferative diabetic retinopathy, especially with baseline diabetic macular edema.

To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes.Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls.A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61-18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73-1.23]) or serum UA (0.90 [95% CI, 0.66-1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12-1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99-1.83]). If aqueous UA (2.46 mg/dL) and aqueous glucose (6.43 mmol/L) were used as reference, high UA (≥2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (≥6.43 mg/dL) alone was not associated with DME.Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.

To investigate, by means of spectral domain optical coherence tomography, retinal reflectivity changes as an early biomarker anticipating radiation-induced macular edema (ME) in patients treated by iodine-125 (I-125) brachytherapy.Thirty patients planned for I-125 brachytherapy because of uveal melanoma were prospectively included and followed every 4 months for five years. Reflectivity alterations, namely hyperreflective retinal foci, were characterized and counted by two independent masked examiners by means of spectral domain optical coherence tomography imaging. Hyperreflective retinal foci were defined as discrete intraretinal reflectivity changes ≤30 µm, with reflectivity similar to nerve fiber layer and without back shadowing.Macular edema occurred in 17 patients (24.2 ±15.1 months) (group 1) after irradiation. Thirteen patients showed no signs of ME at the 5-year follow-up (group 2). The number of hyperreflective retinal foci was statistically higher in sequential visits until the evidence of ME in group 1 vs group 2 (P0.0001). In group 1, hyperreflective retinal foci at the follow-up before the evidence of ME were significantly related to the OCT central subfield thickness at ME appearance (P = 0.0002, r2=0.6129). The intergrader agreement was almost perfect (intraclass correlation coefficient = 0.80).Hyperreflective retinal foci may be considered as an early in vivo imaging biomarker of retinal inflammatory response to ocular irradiation, anticipating the development of radiation maculopathy.

The aim of our prospective off-label, interventional clinical trial was to evaluate the efficacy and safety of the fluocinolone-loop-anchoring technique over two years in eyes with iris-lens diaphragm disruption and pseudophakic cystoid macular edema.In 10 eyes, scleral fixation of fluocinolone implant was performed. Main outcome measures were the development of best-corrected visual acuity (BCVA), central retinal thickness over 24 months, and general safety of the procedure.A significant improvement to 0.57 ± 0.38 log MAR (Snellen 20/80) (range 0-1.30) was observed (P = 0.003) at 1 month. Further improvement to 0.45 ± 036 log MAR (Snellen 20/60) was observed until month 18 (P = 0.081). Mean central retinal thickness decreased by 22% from 601.6 ± 235.5 µm to 449.1 ± 128.9 µm at 1 month. In one patient, the implant has to be removed at Month 7 because of elevated intraocular pressure and one patient after globe rupture had a retinal redetachment at Month 4.In this study, we showed that the treatment of recalcitrant pseudophakic cystoid macular edema with scleral fixated fluocinolone implant in eyes with disruption of the iris-lens diaphragm provides good anatomical and functional results with a reasonable safety profile over 24 months in eyes where pseudophakic cystoid macular edema is otherwise difficult to treat and often left untreated.

PURPOSE To describe uveitis cases after the BNT162b2 mRNA SARS-CoV-2 vaccination. METHODS This is a multicenter, retrospective study. Vaccine-related uveitis diagnosis was supported by the classification of the World Health Organization Adverse Drug Terminology and the Naranjo criteria. RESULTS Twenty-one patients (23 eyes) with a mean age of 51.3 years (23-78 years) were included. Eight of the 21 patients had a known history of uveitis. The median time from previous to current attack was 1 year (0.5-15 years). There were 21 anterior uveitis cases, two with bilateral inflammation. Eight cases occurred after the first vaccination and 13 after the second vaccination. All but three presented as mild to moderate disease. Two patients developed multiple evanescent white dot syndrome after the second vaccination. The mean time from vaccination to uveitis onset was 7.5 ± 7.3 days (1-30 days). At final follow-up, complete resolution was achieved in all but two eyes, which showed significant improvement. One case of severe anterior uveitis developed vitritis and macular edema after the second vaccination, which completely resolved after an intravitreal dexamethasone injection. CONCLUSION Uveitis may develop after the administration of the BNT162b2 mRNA vaccine. The most common complication was mild to moderate anterior uveitis, while multiple evanescent white dot syndrome can also occur less frequently.

PURPOSE To assess the incidence of cystoid macular edema (CME) associated with 4-point Gore-Tex suture intraocular lens (IOL) scleral fixation, before and after institution of routine intravitreal triamcinolone acetonide prophylaxis and long-term topical nonsteroidal anti-inflammatory drug usage. METHODS Consecutive patients were included after IOL implantation with concurrent pars plana vitrectomy for spontaneous IOL dislocation due to pseudoexfoliation syndrome. We compared short-term prophylactic nonsteroidal anti-inflammatory drugs only (Group A) to prophylactic intravitreal triamcinolone acetonide and long-term nonsteroidal anti-inflammatory drugs (Group B). RESULTS Twenty-six eyes of 26 patients with pseudoexfoliation syndrome and spontaneous IOL dislocation were studied. Mean logMAR visual acuity improved from 1.27 ± 0.80 (20/375 Snellen equivalent) preoperatively to 0.46 ± 0.39 (Snellen 20/43) postoperatively (P < 0.001). Visual outcomes were similar for Groups A and B. In Group A, 10/16 eyes had CME, 4/16 had chronic CME longer than 6 months, and 1 longer than 12 months. In Group B, 1/10 had CME (which was both chronic and refractory). CONCLUSION In eyes with pseudoexfoliation syndrome and spontaneous IOL dislocation, 4-point Gore-Tex suture IOL ab externo fixation yielded good visual outcomes, although CME was observed more than reported elsewhere. Prophylactic intravitreal triamcinolone acetonide and long-term nonsteroidal anti-inflammatory drugs seem to reduce the risk of postoperative CME.

PURPOSE To identify factors predicting the recurrence of macular edema after the discontinuation of intravitreal antivascular endothelial growth factor injection in patients with branch retinal vein occlusion. METHODS This retrospective study included only subjects who had discontinued injections at 3 months after the final bevacizumab injection due to fully resolved macular edema. Fifty-two eyes meeting the criteria were included in the study and divided into two groups (recurrence and no recurrence). Clinical features and measurements of retinal thickness at the time of the diagnosis and when the decision to stop injections was made (stopping point) were analyzed. RESULTS At the stopping point, the no recurrence group showed a thinner parafoveal inner retina, better best-corrected visual acuity, and lower incidence of ellipsoid zone disruption in multivariate logistic regression analysis (all P < 0.05). Similarly, parafoveal inner retinal thinning of more than 30 µm, when compared with the corresponding region of the fellow eye or the unaffected region of the affected eye, was significantly related to less recurrence of macular edema. CONCLUSION Thinning of the parafoveal inner retina as well as better vision and intact outer retinal layers are associated with a lack of recurrence of macular edema. These findings suggest that inner retinal atrophy after branch retinal vein occlusion may result in a reduction in oxygen demand in the affected retinal tissue and less production of vascular endothelial growth factor.

PURPOSE: To assess the impact of histogram adjustments and binarization thresholding selection on quantitative measurements of diabetic macular ischemia using optical coherence tomography angiography (OCTA). METHODS: Patients with diabetic retinopathy (DR) who had swept-source OCTA imaging obtained were enrolled. An additional group of 15 healthy control subjects was included for comparison. Previously used brightness/contrast changes and binarization thresholds were applied to original OCTA images to obtain and compare different binarized images. Qualitative and quantitative comparisons were performed. RESULTS: Thirty patients with DR (30 eyes) were included in the analysis. Fifteen eyes displayed the presence of diabetic macular edema. Qualitative grading revealed that binarized images obtained using a global threshold had better quality compared with local or multistep thresholds. The "median" filter was most frequently graded as the histogram adjustment resulting in binarized images with best quality. In the quantitative analysis, local thresholds tended to generate higher values of measured metrics. Differences in OCTA metrics between global and local thresholds were associated with presence of diabetic macular edema and signal strength index value. In the comparison between healthy and DR eyes, differences in OCTA metrics were significantly affected by binarization threshold selection. CONCLUSION: Quantitative OCTA parameters may be significantly influenced by strategies to quantify macular perfusion. Image quality and presence of macular edema can significantly impact OCTA-derived quantitative vascular measurements and differences between global and local binarization thresholds. These findings highlight the importance of consistent strategies to reliably generate quantitative OCTA metrics in patients with DR.

PURPOSE: Two-dimensional (2D) optical coherence tomography angiography (OCTA) is known to be prone to segmentation errors, especially in pathologic eyes. Therefore, our aim was to systematically compare intrasession repeatability between repeated scans for 2D and three-dimensional (3D) OCTA metrics in quantifying retinal perfusion in eyes with diabetic macular edema. METHODS: Diabetic patients with diabetic retinopathy and diabetic macular edema who had two consecutive OCTA imaging scans obtained during the same visit were retrospectively included. A previously validated algorithm was applied to OCTA volume data to measure the 3D vascular volume and perfusion density. Optical coherence tomography angiography en face images were also processed to obtain 2D perfusion density metrics. RESULTS: Twenty patients (20 eyes) with diabetic retinopathy and diabetic macular edema were included. The intraclass correlation coefficient ranged from 0.591 to 0.824 for 2D OCTA metrics and from 0.935 to 0.967 for 3D OCTA metrics. Therefore, compared with the 2D OCTA analysis, the intraclass correlation coefficients of the 3D OCTA analysis were higher (without overlapping of the 95% confidential intervals). Similarly, the coefficient of variation (ranging from 2.2 to 4.2 for 2D OCTA metrics and from 1.9 to 2.0 for 3D OCTA metrics) indicated that the 3D OCTA-based quantifications had the highest interscan intrasession agreements. Differences in interscan 2D OCTA metrics' values were associated with average macular volume. CONCLUSION: Three-dimensional OCTA metrics have higher values of intrasession repeatability, as compared with 2D OCTA metrics. The latter finding seems to be related to the high rate of segmentation errors occurring in diabetic macular edema eyes.

PURPOSE To compare the efficacy and safety between lens-sparing vitrectomy and phacovitrectomy for primary rhegmatogenous retinal detachment treatment according to surgical experience. METHODS We retrospectively reviewed the medical records of 193 patients with primary rhegmatogenous retinal detachment who underwent either lens-sparing vitrectomy (n = 111) or phacovitrectomy (n = 82). Patients were operated by two experienced surgeons or eight vitreoretinal fellows and had a minimum follow-up of 6 months. Anatomical success rate, postoperative complications, and functional outcomes were compared. RESULTS Primary anatomical success rate was 92.8% (103/111) for lens-sparing vitrectomy and 91.5% (75/82) for phacovitrectomy (P = 0.733). The fellows had lower success rate after phacovitrectomy compared with the experts, but not statistically significant (85% [34/40] vs. 97.6% [41/42], P = 0.054). During phacovitrectomy, one zonulysis case in the experts group and four posterior capsular rupture cases in the fellows group were noted. Cystoid macular edema was found only after phacovitrectomy (12.2% [10/82]), and epiretinal membrane occurred more after phacovitrectomy than after lens-sparing vitrectomy (28% [23/82] vs. 8.1% [9/111], P < 0.001). There was no difference in the occurrence of cystoid macular edema and epiretinal membrane after phacovitrectomy between two surgeon groups (P = 0.514, 0.701, respectively). CONCLUSION Combined phacoemulsification and vitrectomy has no additional benefit in improving the surgical outcome of primary rhegmatogenous retinal detachment management. Considering the intraoperative and postoperative complications and the relatively low success rate, phacovitrectomy may not be a desirable option in inexperienced surgeons.

PURPOSE To investigate the types of intraretinal cysts that are associated with epiretinal membranes and to evaluate the effects of each type of intraretinal cyst on postoperative outcomes. METHODS Retrospective, cross-sectional study design. Patients who underwent preoperative fluorescent angiography and epiretinal membrane surgery from February 2014 to May 2019 were included. Intraretinal cysts were subdivided into cystoid macular edema with angiographic leakage and microcystic macular edema (MME) without angiographic leakage. RESULTS A total of 100 eyes from 100 patients were enrolled. Intraretinal cysts were present in 54 (54.0%) eyes before surgery, of which 27 (27.0%) eyes showed MME, 18 (18.0%) eyes showed cystoid macular edema, and 9 (9.0%) eyes showed cystoid macular edema and MME. After surgery, the number of eyes with cystoid macular edema decreased significantly (P < 0.001), whereas the number of eyes with MME did not (P = 0.302). Absence of preoperative MME, poorer initial visual acuity, increased central foveal thickness, and intact ellipsoidal zone were associated with favorable visual recovery (P = 0.035, 0.033, 0.018, and 0.035, respectively). CONCLUSION Microcystic macular edema associated with epiretinal membranes was a poor prognostic factor for epiretinal membrane surgery. The persistent existence of MME after surgery affirms related chronic structural changes. Further studies should investigate whether earlier surgical intervention (possibly before the development of MME) benefits visual outcomes.

PURPOSE Visual outcomes after postinjection endophthalmitis have been well-studied, but the effect of endophthalmitis on the underlying exudative disease process remains unclear. We investigate the need for continued anti-vascular endothelial growth factor injections after endophthalmitis. METHODS Eyes that developed endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor between January 1, 2016, and May 31, 2018, at a single academic retina practice were identified. Retrospective chart review was performed to determine 1) the proportion of eyes without recurrence of macular edema or subretinal fluid after endophthalmitis and 2) the proportion achieving a 12-week or greater interval between anti-vascular endothelial growth factor injections or exudation after endophthalmitis compared with internal controls before endophthalmitis. RESULTS Of 50 eyes with endophthalmitis, seven (14.0%) had no fluid recurrence at a mean of 98.1 week. Of 43 eyes with recurrence, 48.0% achieved a >12-week recurrence-free interval after endophthalmitis (vs. 8.3% before endophthalmitis; P < 0.0001). Eyes with compared to those without choroidal neovascularization were more likely to achieve this interval (60.5% vs. 8.3%, respectively; P = 0.002). CONCLUSION Endophthalmitis after anti-vascular endothelial growth factor injection is associated with relative stability of the underlying exudation. Further research is necessary to elucidate the mechanism, which may be useful in developing strategies and targets for the treatment of exudative macular diseases.

PURPOSE To identify risk factors for incorrect self-identification of the treatment eye before intravitreal injections. METHODS This prospective study included consecutive patients who were asked to designate the eye for which the intravitreal injection was intended and were subsequently divided into two groups according to whether or not they identified the correct eye. RESULTS Overall, 349 eyes (n = 349) were included, and 8.6% (n = 30) designated the incorrect eye or did not know which eye was intended for treatment. Incorrect designation was associated with diabetic macular edema (odds ratio [OR] = 0.33 [0.15-0.75]), first injection in the intended eye or ≥1 year since previous injection (OR = 0.34 [0.14-0.87]), Arabic native tongue (OR = 0.48 [0.22-1.01]), previous injection to the fellow eye (OR = 0.26 [0.10-0.64]), and concurrent treatment of both eyes (OR = 0.35 [0.16-0.74]). Multivariate analysis showed the first injection or ≥1 year since last injection in the treatment eye (R2 = 2.24%, P = 0.004, OR = 0.20 [0.07-0.57]) and previous injection in the fellow eye (R2 = 6.55%, P < 0.001, OR = 0.20 [0.07-0.52]) as significant independent predictors of incorrect identification. CONCLUSION Several factors are associated with a greater probability for incorrect patient's self-identification of the eye laterality intended for intravitreal injections. These findings may help identify patients with a higher risk of such potential errors.

PURPOSE To evaluate the benefits of internal limiting membrane peeling in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for the treatment of vitreous hemorrhage. METHODS Two hundred and fifty-eight proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for vitreous hemorrhage were enrolled into the trial. Patients were randomized into one of two cohorts: Group A patients underwent internal limiting membrane peeling, whereas Group B patients did not undergo internal limiting membrane peeling. The main outcome was best-corrected visual acuity at 6 months. Secondary outcomes were optical coherence tomography central macular thickness at 6 months, incidence of diabetic macular edema treatment during the postoperative trial period, and incidence of epiretinal membrane at 6 months. RESULTS Two hundred and seven patients were randomized and completed 6 months follow-up. Group A had better best-corrected visual acuity at 6 months than Group B (P < 0.01). Group A had a lower incidence of diabetic macular edema treatment during the postoperative trial period and a lower incidence of epiretinal membrane at 6 months than Group B (P = 0.02 and P < 0.001, respectively). There was a trend toward lower central macular thickness on optical coherence tomography in Group A than Group B (P = 0.09). There were no significant differences in baseline details or complications intraoperatively or postoperatively between cohorts. CONCLUSION This trial demonstrated better vision, fewer postoperative diabetic macular edema treatments, and a lower incidence of epiretinal membrane at 6 months when internal limiting membrane peeling was performed. Internal limiting membrane peeling may be considered a vital maneuver to perform in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for vitreous hemorrhage.

PURPOSE To evaluate microstructural changes in cystoid macular edema in retinitis pigmentosa after intravitreal dexamethasone implant injection. METHODS In an extended cohort of a randomized trial of intravitreal dexamethasone implant for the management of retinitis pigmentosa-associated cystoid macular edema, microstructural changes during six months after the treatment were evaluated using spectral-domain optical coherence tomography. RESULTS Forty-two eyes were included, and all had cystoid space in the inner nuclear layer (INL) at baseline. No eyes showed subretinal fluid, and 28.6% showed hyperreflective foci. Among 38 eyes with cystoid space both in the INL and outer nuclear layer/Henle's layer, 13 (34.2%) showed complete resolution and 12 (31.6%) showed cystoid space only in the INL at 2 months after injection, whereas others showed persistent cystoid space in both layers. After complete resolution, cystoid space recurrence was earlier in the INL than in the outer nuclear layer/Henle's layer. Multivariable analysis showed that greater cystoid space area in the INL and outer nuclear layer/Henle's layer, presence of macular leakage, and longer intact external limiting membrane at baseline were associated with greater cystoid space area decrease after the treatment. CONCLUSION Resolution and recurrence pattern of retinitis pigmentosa-associated cystoid macular edema after dexamethasone treatment showed that the INL is the primary layer of cystic change, and this suggests its pathogenesis is most likely caused by Muller cell dysfunction.

PURPOSE To show the long-term effect of cystotomy with or without fibrinogen clot removal for refractory cystoid macular edema secondary to diabetic retinopathy. METHODS Retrospective analyses of the medical records of 30 eyes of 30 patients with refractory cystoid macular edema secondary to diabetic retinopathy who had followed up for 12 months after the surgery were performed. RESULTS There were 15 men and 15 women. The mean ± SD age was 68.4 ± 7.9 years. The best-corrected visual acuity (logarithm of the minimal angle of resolution) at 12 months after the surgery (0.33 ± 0.25, Snellen equivalent, 20/42) was statistically better than the preoperative best-corrected visual acuity (0.45 ± 0.33, Snellen equivalent, 20/56) (P < 0.01). The central sensitivity on microperimetry (dB) was not statistically changed between preoperatively (24.0 ± 4.9) and 12 months after the surgery (24.1 ± 4.0) (P = 0.75). The central retinal thickness on optical coherence tomography (μm) at 12 months after the surgery (300.3 ± 99.0) was statistically improved compared with the preoperative central retinal thickness (565.6 ± 198.7) (P < 0.01). During the follow-up period, cystoid macular edema relapsed in seven of 30 eyes. The preoperative cystoid cavity reflectivity on optical coherence tomography in patients with fibrinogen clot removal (n = 16) was significantly higher than that in patients without fibrinogen clot removal (n = 14) (P < 0.04). CONCLUSION The cystotomy with or without fibrinogen clot removal may be a promising treatment option for refractory cystoid macular edema secondary to diabetic retinopathy.

PURPOSE: To describe our managing strategy for COVID-19 emergency, to evaluate the adherence to intravitreal treatment (AtT) rate during the outbreak in a referral hospital in Milan, and to correlate it with patients' clinical features. METHODS: The AtT rate of patients with scheduled intravitreal injections during the COVID-19 outbreak from February 23, 2020 to March 31, 2020 was compared with the previous trimester and with March 2019. The impact of age, sex, visual function, and diagnosis on the AtT rate during unlocked/locked weeks (from March 8th) was evaluated. RESULTS: Of 650 consecutive patients with scheduled intravitreal injections, the AtT rate during the COVID-19 outbreak was 0.37. This was significantly lower compared with AtT registered in the previous trimester (0.92) and in the same weeks in 2019 (0.90) (both P < 0.001). Patients adherent to treatment were significantly younger (P < 0.001) and had a lower best-corrected visual acuity in the fellow eye (P = 0.046). During the lockdown weeks, the AtT rate was significantly lower than in the two unlocked weeks (0.19 vs. 0.73, P < 0.001). In addition, the AtT rate in patients classified as "emergent"" during the lockdown weeks was 0.60. CONCLUSION: These preliminary results can help the retina specialist community to foresee this unique scenario and to develop successful management strategies."

Purpose This study aimed to investigate the effect of intravitreal conbercept (IVC) injections on the aqueous humor concentrations of angiogenic and inflammatory cytokines in patients with macular edema (ME) due to central retinal vein occlusion and to determine whether changes in cytokine levels after IVC are associated with the development of rebound ME. Methods Forty-nine patients with ME caused by central retinal vein occlusion were included in this retrospective study. Monthly doses of IVC were administered for three months, followed by a Pro Re Nata dosing regimen. Rebound ME was defined as ≥110% increase in the foveal thickness compared with the baseline. Whenever injections were administered, aqueous humor samples were obtained. Multiplex bead assay was used to measure seven angiogenic and inflammatory cytokines in aqueous humor samples. Results At baseline, patients with central retinal vein occlusion showed significantly higher aqueous humor concentrations of vascular endothelial growth factor, placental growth factor, monocyte chemoattractant protein-1, platelet-derived growth factor-AA, IL-6, IL-8, and IL-12. At 1-month and 2-month follow-up after IVC, significantly decreased concentrations of all cytokines were observed. During the 12-month follow-up period, 6 of the 49 eyes (12.2%) showed rebound ME after IVC. Patients with rebound ME showed significantly elevated levels of inflammatory but not angiogenic cytokines. Conclusion Angiogenic and inflammatory cytokines were overexpressed in patients with ME caused by central retinal vein occlusion. Conbercept treatment influenced the concentrations of various inflammatory cytokines and reduced aqueous vascular endothelial growth factor and placental growth factor concentrations. Rebound ME may occur due to disruption of the balance between angiogenic and inflammatory cytokines and an accompanying excess of inflammatory cytokines but not angiogenic cytokines, after antivascular endothelial growth factor therapy.

Purpose: To evaluate Pegasus optical coherence tomography (OCT), a clinical decision support software for the identification of features of retinal disease from macula OCT scans, across heterogenous populations involving varying patient demographics, device manufacturers, acquisition sites, and operators. Methods: Five thousand five hundred and eighty-eight normal and anomalous macular OCT volumes (162,721 B-scans), acquired at independent centers in five countries, were processed using the software. Results were evaluated against ground truth provided by the data set owners. Results: Pegasus-OCT performed with areas under the curve of the receiver operating characteristic of at least 98% for all data sets in the detection of general macular anomalies. For scans of sufficient quality, the areas under the curve of the receiver operating characteristic for general age-related macular degeneration and diabetic macular edema detection were found to be at least 99% and 98%, respectively. Conclusion: The ability of a clinical decision support system to cater for different populations is key to its adoption. Pegasus-OCT was shown to be able to detect age-related macular degeneration, diabetic macular edema, and general anomalies in OCT volumes acquired across multiple independent sites with high performance. Its use thus offers substantial promise, with the potential to alleviate the burden of growing demand in eye care services caused by retinal disease.

To evaluate the efficacy and safety of intravitreal dexamethasone (DEX) implant in retinitis pigmentosa patients with cystoid macular edema (CME).In this randomized, noncontrolled, paired-eye, single crossover clinical trial, one eye of retinitis pigmentosa patients with bilateral CME with central macular thickness of250 µm was randomized to intravitreal DEX implant while the fellow eye was observed. Both eyes were started on topical dorzolamide. At Month 6, DEX implant was eligible for both eyes when CME was250 µm. Patients were followed up until Month 12. Primary outcome measures were the central macular thickness and best-corrected visual acuity changes from baseline at Month 2.Fourteen patients with bilateral RP-CME were included. Study eyes showed significant central macular thickness decrease (median, -147.5 µm; P = 0.001) and best-corrected visual acuity improvement (median, +6 letters; P = 0.001) at Month 2, but not at Month 6. Intravitreal DEX implant at Month 6 produced comparable efficacy to baseline treatment in 11 fellow eyes and 12 study eyes. Topical dorzolamide did not show significant therapeutic efficacy. During 12 months, elevated intraocular pressure of21 mmHg and cataract progression were observed in 14.3% and 40.0% of study eyes.Intravitreal DEX implant can both reduce macular thickness and improve vision in RP-CME, while repeated injection is required.

PURPOSE To study the role of serum biomarkers as prognostic factors for qualitative and quantitative response to anti-vascular endothelial growth factor injections for diabetic macular edema (DME). METHODS Sixty-seven eyes with DME were treated with intravitreal bevacizumab during a 12-month follow-up period. All cases underwent a baseline workup consisting of 12 inflammatory, metabolic and prothrombotic factors. The following outcomes were evaluated at 3-month intervals until 1 year of follow-up: visual acuity, central subfield thickness (CST), macular volume (MV), % of change from baseline in CST, occurrence of a CST change 20%, and a CST

Purpose To investigate the effect of age on aflibercept (Eylea) response in macular edema secondary to treatment-naive diabetic eyes. Methods Two hundred seventy-three eyes of 273 treatment-naive patients with macular edema secondary to diabetes mellitus were enrolled in this study. The patients in the study were divided into the following 4 groups according to their ages: Group 1 (40-50 years), Group 2 (51-60 years), Group 3 (61-70 years), and Group 4 (>70 years). Three consecutive injections at intervals of 1 month were applied to all diabetic patients. The efficacy of the aflibercept treatment on macular edema according to age groups was assessed by optical coherence tomography by comparing the central foveal thickness (CFT) values and mean visual acuity changes after initial and three loading dose injections. Results After three consecutive aflibercept injections, the mean reduction of CFT in Groups 1, 2, 3, and 4 were -256.4 ± 110.9, -197.4 ± 96.4, -189.4 ± 110.8, and -186.2 ± 118.9 µm, respectively. The changes of CFT was significantly different between age groups (P = 0.003, analysis of covariance). The improvement of visual acuity was significantly different in each group (P Conclusion In this study, it was observed that the efficacy of aflibercept treatment was found to be more effective in younger patients in treatment-naive diabetic macular edema patients.

Purpose To establish the prevalence and risk factors for intravitreal dexamethasone implant migration into the anterior chamber in eyes with macular edema. Methods This was a multicenter, retrospective, observational chart review of data that included patients with macular edema who had been treated with at least one intravitreal dexamethasone injection. Patients with incomplete chart information during the follow-up period were excluded. Results The prevalence of implant migration in 468 patients, considering the number of injections, was 1.6%, with significant associations between implant migration and cataract surgery (P = 0.043) and intraocular lens status (P = 0.005) and a trend toward statistical significance (P = 0.057) with vitrectomy. A higher rate of implant migration into the anterior chamber was observed in vitrectomized eyes (4.8%) when compared with patients who did not undergo a vitrectomy (1.6%). The implants that migrated were removed with forceps with/without viscoelastic expression or with 20-gauge cannulas connected to the vitreous cutter machine. Conclusion The risk of implant migration into the anterior chamber was 1.6%. Risk factors were a history of cataract surgery or vitrectomy and aphakia. When anterior migration occurs, rapid removal is advised, especially if corneal edema is present.

Purpose To report the 1-year outcomes of a novel surgical technique for the fixation of a CZ70BD intraocular lens with Gore-Tex suture using cow-hitch knots. Methods A retrospective chart review of 15 patients (13 men and 2 women) who underwent fixation of a posterior chamber intraocular lens with Gore-Tex suture was performed. Short- and long-term outcomes data were collected 1 month and 1 year after surgery, respectively. Results Fourteen of the 15 patients met inclusion criteria and were included in the analysis. Mean visual acuity improved significantly from Snellen 20/491 preoperatively to Snellen 20/59 at postoperative month 12 (P = 0.002). The most common short-term complications included increased intraocular pressure (n = 6) and cystoid macular edema (n = 4). The most common long-term complications included increased intraocular pressure (n = 2) and iris capture of the intraocular lens (n = 2). Conclusions One-year outcome data suggest that this technique is a reasonable surgical option for secondary intraocular lens placement in patients who lack capsular support.

PURPOSE To evaluate the influence of silicone oil (SO) tamponade on retinal layers thickness and visual acuity in patients who underwent pars plana vitrectomy for rhegmatogenous retinal detachment. METHODS This is a retrospective case series of consecutive patients who underwent pars plana vitrectomy for rhegmatogenous retinal detachment with SO tamponade. Visual acuity and central macular thickness were measured with SO and at least a month after SO removal (SOR). Patients with insufficient or poor-quality images or macular pathologies such as macular edema or epiretinal membranes were excluded. RESULTS Forty-one patients with an average age of 56.1 ± 15.2 years were included, and 54% presented with fovea ON. Average tamponade duration was 151 ± 54 days. Central macular thickness of the operated eye increased from 249 ± 50 µm before to 279 ± 48 µm after SOR (P < 0.001), compared with 281 ± 21 µm of the fellow eye (P < 0.001). A mean change of 26 µm was found in the internal layers (P < 0.001). Visual acuity improved from 0.85 ± 0.97 logarithm of the minimal angle of resolution (logMAR; Snellen 20/140) with SO tamponade to 0.34 ± 0.28 logMAR (Snellen 20/43) after SOR (P < 0.001). For patients with fovea ON and without significant cataract, visual acuity was 0.19 ± 0.16 logMAR (Snellen 20/30) at presentation, 0.59 ± 0.41 logMAR (Snellen 20/80) with SO (P = 0.005), and 0.18 ± 0.15 logMAR (Snellen 20/30) after SOR (P = 0.003). CONCLUSION Silicone oil tamponade causes a transient decrease in central macular thickness, mainly in the inner layers. After SOR, central macular thickness resembles to the fellow eyes. The mechanism for this effect is unclear, but apparently has no influence on final visual acuity.

Purpose To evaluate the effect of cataract extraction (CE) by phacoemulsification on the vitreomacular interface (VMI) of eyes with preexisting vitreomacular traction (VMT). Methods Retrospective, observational case series. Patients with VMT who elected to proceed with CE, before any vitreoretinal intervention, were studied. Eyes with at least a 12-month follow-up period were included. The status of the vitreomacular adhesion at different time points was assessed using spectral-domain optical coherence tomography. The best-corrected visual acuity was recorded at different time points. Other macular and systemic comorbidities were documented. Results Fifteen eyes from 15 phakic patients with symptomatic VMT were included. Six of them were male subjects. Seven patients had diabetes mellitus and two of them also had nonproliferative diabetic retinopathy. The preoperative macular comorbidities included macular hole in six eyes (Stage 1 in 3 eyes and Stage 2 or 3 in another 3 eyes), epiretinal membrane in five eyes, and cystoid macular edema in four eyes. After uncomplicated CE, the VMT was released in 5 eyes, whereas in 10 eyes, CE did not significantly change the status of the vitreomacular adhesion. Three of 3 eyes with preexisting full-thickness macular hole (Stage 2 or 3 macular hole) were found to have Stage 4 macular hole shortly after CE. In seven of seven patients with diabetes mellitus, the status of the vitreomacular interface did not change after CE. Eventually, 7 of 15 patients underwent additional pars plana vitrectomy. Compared with the baseline vision, and vision before other interventions, the visual acuity after CE improved in 5 patients, remained unchanged in 7 patients, and decreased in the 3 patients with Stage 2 or 3 macular hole. The mean preoperative and early postoperative visual acuity was 20/59 and 20/68, respectively (P > 0.05). Conclusion The effect of CE in phakic eyes with known VMT varies significantly. In the current case series, every eye with VMT and Stage 2 or 3 macular hole ended up with Stage 4 macular hole, although the VMT did not change significantly in the eyes of diabetic patients. Studies with larger sample size are needed to further elucidate the impact of elective CE on VMT.

International audience; Purpose: Macular edema is a common retinal disease which may leave important anatomical and functional sequelaes. Directional fundus imaging consists of comparing on- and off-axis images to reveal angle-dependent reflectance properties of fundus structures, which may be related to misaligned photoreceptors. Here, we analyzed directional optical coherence tomography (OCT) and flood-illumination adaptive optics ophthalmoscopy images to detect evidence of misaligned photoreceptors following macular edema.Methods: Transversal, observational study. Nine patients having recovered a normal macular profile after macular edema due to retinal vein occlusion were included. For each patient, a reference OCT scan (i.e., with the incident beam normal to the fovea) was acquired, and off-axis scans were then acquired by laterally shifting the entry pupil. In addition, in four of these eyes, directional adaptive optics ophthalmoscopy documented the directional variations of cone metrics.Results: Included patients comprised two women and seven men (age range, 19–76 years). Reference OCT scans showed patchy attenuation of the cone outer segment tips and to a lesser extent of the inner segment/outer segment lines in all, but two eyes; these. Increased intensity of the cone outer segment tips and inner segment/outer segment lines could be observed on off-axis scans. Accordingly, fusion images showed 66% average reduction of the length of cone outer segment tips attenuation. In two cases, although reference scans showed continuity of outer bands, focal attenuation was evidenced in off-axis images. Directional adaptive optics ophthalmoscopy imaging showed a strong directional variability of cone counts in these areas, ranging from near absence to roughly two-third of reference values. In each case, directional variations of cone counts paralleled those of the reflectance of outer bands.Conclusion: After macular edema, focal attenuations of the inner segment/outer segment and of the cone outer segment tips lines may be present on OCT. These areas may show a strong directional variability by both OCT and adaptive optics ophthalmoscopy, suggesting that misaligned photoreceptor outer segments contribute to such features. The evaluation of outer retinal damage following macular edema should therefore take into account the optical Stiles–Crawford effect to disambiguate missing from misaligned cones.

Purpose To report the incidence and course of ocular hypertension after intravitreal injection of 2-mg triamcinolone acetonide (IVT). Methods In a retrospective, consecutive series, all patients receiving 2-mg IVT at a single institution between March 1, 2012, and March 1, 2017, with a minimum of 3-month follow-up were reviewed. Ocular hypertension was defined as an intraocular pressure (IOP) measurement over 24 mmHg at any follow-up visit after IVT. Patients receiving topical, periocular, or intravitreal corticosteroid other than 2-mg IVT were excluded. Results A total of 106 eyes in 100 patients receiving at least one injection of 2-mg IVT were included. Eyes received an average of 2.9 injections (range 1-17), and average patient follow-up was 15.1 months (range 3.0-52.5 months). A total of 14 eyes (13.2%) in 14 patients developed ocular hypertension after a median of 1.5 injections (range 1-9) with an average peak IOP of 29 mmHg (range 25-38 mmHg). Overall, a total of 11 eyes (10.4%) had an IOP elevation ≥10 mmHg above baseline at any point after first IVT. In all cases of ocular hypertension, IOP was successfully managed with observation or topical IOP-lowering medication alone; no patients required surgical intervention. Conclusion Ocular hypertension developed in 13.2% of eyes receiving intravitreal injection of 2-mg triamcinolone acetonide. Incidence of ocular hypertension after 2-mg IVT compares favorably with other intravitreally administered corticosteroids.

To compare the efficacy of intraoperative intravitreal dexamethasone implant for macular edema secondary to diabetic retinopathy (DME), retinal vein occlusion (RVO), and noninfectious posterior uveitis.A retrospective review of 62 patients (29 men and 33 women; mean age 51.19 ± 14.41 years; 65 eyes) was performed. Best-corrected visual acuity (in logarithm of the minimal angle of resolution), central foveal thickness, intraocular pressure, and postoperative edema-free period were postoperatively assessed up to 1 year. The preoperative and postoperative numbers of other intravitreal injections needed were compared.Best-corrected visual acuity gradually improved in the DME group (from 0.87 to 0.51) but failed to improve from Month 3 onward in the RVO and uveitis groups. Central foveal thickness decreased in all groups, especially in the DME group (from 550.93 to 338.10 μm). Edema-free period was longest in the DME group (19.34 ± 15.12 months), followed by the uveitis (12.91 ± 7.85 months) and RVO (8.50 ± 8.76 months) groups. Subjects in the uveitis group used more intraocular pressure-lowering agents (1.00 ± 1.27) than those in the DME (0.13 ± 0.49) and RVO (0.36 ± 0.79) groups. Increased intraocular pressure events were most frequent in postoperative Week 1, especially in the uveitis group.Vitrectomy combined with intravitreal dexamethasone implant for DME, RVO, and noninfectious posterior uveitis had a favorable clinical outcome.

PURPOSE To determine factors associated with 360-degree laser retinopexy (360LR) during primary pars plana vitrectomy ± scleral buckle for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. METHODS This is a multicenter, retrospective, interventional study. Patients undergoing primary pars plana vitrectomy or primary pars plana vitrectomy + scleral buckle for noncomplex primary RRD in 2015 were evaluated. Primary outcomes were single surgery anatomical success (SSAS) and final anatomical success. Secondary outcomes included final logarithm of the minimum angle of resolution visual acuity, epiretinal membrane formation, cystoid macular edema development, and number of subsequent vitrectomies. Multivariate regressions were performed. RESULTS Two thousand two hundred and forty-eight surgeries by 61 surgeons were included; of which, 516 underwent 360LR. Younger age (P = 0.01), more retinal breaks (P = 0.01), more extensive RRD (P < 0.001), and surgeon ID (P < 0.001) were significantly associated with 360LR. No significant associations between 360LR and single surgery anatomical success (P = 0.44), epiretinal membrane formation (P = 0.14), cystoid macular edema development (P = 0.28), or number of subsequent vitrectomies (P = 0.41) were found. Controlling for case complexity, 360LR was significantly associated with lower final anatomical success (P < 0.001) and worse final logarithm of the minimum angle of resolution visual acuity (P < 0.001). CONCLUSION Multiple factors influenced whether 360LR was performed during primary pars plana vitrectomy ± scleral buckle for RRD. However, 360LR was not associated with improved surgical outcomes, and in fact, it may be associated with poorer outcomes.

PURPOSE To evaluate effects of reimbursement policy change on visual outcomes of patients with diabetic macular edema treated with ranibizumab. METHODS In this retrospective comparative cohort study, we included 78 treatment-naive patients with diabetic macular edema (107 eyes) insured under Taiwan's National Health Insurance from July 2013 to January 2015 (Group A) and April 2016 to June 2017 (Group B), or before and after the major reimbursement policy change, respectively. Best-corrected visual acuity (BCVA), optical coherence tomography findings, and injection numbers at baseline and postinjection Months 3, 6, and 12 were collected. Mean BCVA change and predictive factors for enhanced BCVA improvement at Month 12 were analyzed. RESULTS The mean improvement in BCVA at 1 year was 5.8 ETDRS letters (Group A) before and 14.8 letters (Group B) after the policy change (P = 0.009), and the mean numbers of injections were 4.6 ± 2.0 and 6.5 ± 2.3 in Group A and B (P < 0.001), respectively. Linear regression revealed that greater visual improvement at Month 12 was significantly associated with worse baseline BCVA, greater visual gain at Month 3, new reimbursement policy (Group B), and the presence of subretinal fluid in baseline optical coherence tomography, but not with total injection number. Compared with Group A, Group B had enhanced BCVA improvement when baseline subretinal fluid was present (P = 0.001), but not when subretinal fluid was absent (P = 0.656). CONCLUSION Health care policy change significantly affected the visual outcomes of patients with diabetic macular edema in a clinical practice setting, with superior final BCVA and BCVA improvement after increased reimbursement. Presence of subretinal fluid at baseline predicted enhanced post-policy change visual improvement.

PURPOSE To investigate the spectral domain optical coherence tomography findings before and after dialysis in patients with diabetic end-stage renal disease undergoing dialysis for the first time. METHODS A retrospective medical review of patients with diabetic end-stage renal disease who recently started dialysis was conducted. Spectral domain optical coherence tomography findings before and after initiation of dialysis were analyzed. Systemic blood pressure, body weight, estimated glomerular filtration rate, and serum levels of blood urea nitrogen, creatinine (Cr), albumin, hemoglobin (Hb), and total CO2 were measured before and 1 month after starting dialysis. The correlations between the changes in these variables and the degree of decrease of the central subfield thickness after initiation of dialysis were analyzed. RESULTS A total 26 eyes from 15 patients were included. Among them, 14 started hemodialysis, and 1 started peritoneal dialysis. After initiation of dialysis, the incidence of any macular edema significantly decreased from 69.2% (18/26) to 26.9% (7/26) (P = 0.001). The central subfield thickness (317.92 ± 91.41 vs. 287.77 ± 57.55 μm, P = 0.006) and subfoveal choroidal thickness (313.31 ± 85.89 vs. 288.81 ± 92.02; P = 0.024) also significantly decreased. Improvement in blood urea nitrogen, Cr, Hb, and total CO2 levels in serum and estimated glomerular filtration rate was observed. A significant positive correlation between the amount of central subfield thickness decrease and the decrease in serum blood urea nitrogen was found (Pearson correlation coefficient: 0.481, P = 0.013). CONCLUSION Macular edema and central subfield thickness significantly decreased after initiation of dialysis in patients with diabetic chronic renal failure without any ocular treatment. This may be related to the improvement in uremia and volume overload after the initiation of dialysis.

Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis.Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography.Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µm and 164 µm at Month 1 (P = 0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure.A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.

PURPOSE To evaluate fixation status of eyes with branch retinal vein occlusion (BRVO) and to investigate its association with other clinical parameters. METHODS This study included 57 consecutive eyes with BRVO after resolution of macular edema. Fixation status was determined by microperimetry. Defect length of the foveal ellipsoid zone band was measured by optical coherence tomography, and retinal perfusion status was assessed by optical coherence tomography angiography. RESULTS In microperimetry, the mean fixation rate around the gravitational center of all fixation points (defined as the fixation center) was found to be 79.8 ± 18.9%, which was significantly associated with defect length of the foveal ellipsoid zone band (P < 0.001) and distance between the foveal and fixation centers (P = 0.012). The integrity of the ellipsoid zone band at the fixation center was intact in 55 eyes (96.5%). Fixation centers were located within and outside the foveal avascular zone in 33 (57.9%) and 24 (42.1%) eyes, respectively; among the latter eyes, all fixation centers were perfused. Downward deviation of fixation points was rare, despite variations in the occluded area; there was a significant difference in distribution of deviation between eyes with superotemporal and inferotemporal BRVO (P < 0.001). CONCLUSION In eyes with BRVO, fixation status was strongly associated with visual acuity, morphologic damage, and retinal perfusion status both in the foveal area and at the fixation center after resolution of macular edema. This information regarding fixation status could facilitate vision management in patients with BRVO.

PURPOSE To investigate the imaging characteristics of early Type 3 neovascularization and propose a new pathophysiologic sequence for early disease. METHODS Patients were evaluated with a comprehensive ophthalmologic examination to include fundus photography, optical coherence tomography, optical coherence tomography angiography, fluorescein angiography, and volume-rendered optical coherence tomography angiography. Relevant literature was also reviewed. RESULTS There were 10 eyes of 9 patients who had a mean age of 87 (range 79-93) years and 7 were women. The patients were seen to have distributed areas of cystoid macular edema, not necessarily contiguous with areas of fluorescein or optical coherence tomography angiographic evidence of neovascularization, which colocalized with each other. Areas of hemorrhage were not necessarily contiguous with observed neovascularization. In some patients, massive amounts of edema were imaged, although the associated neovascular invasion was small and did not reach deeper portions of the retina. These findings were readily responsive to intravitreal injections of anti-vascular endothelial growth factor (VEGF) medication. Review of published literature showed conflicting pathophysiologic proposals, which did not abide with contemporaneous imaging findings. CONCLUSION Type 3 neovascularization likely grows in response to increased cytokine levels, particularly VEGF, in a permissive environment. Elevated levels of VEGF have been shown to cause hemorrhage, edema, and telangiectasis in the macula, suggesting some of the manifestations of Type 3 neovascularization are related to increased tissue VEGF levels and not necessarily to the neovascularization alone. A proposal based on imaging and histopathologic findings and known physiologic effects of VEGF is presented.

This study suggests that the combination therapy of intravitreal ranibizumab and 577-nm subthreshold micropulse photocoagulation can treat macular edema secondary to macular edema secondary to branch retinal vein occlusion effectively, by decreasing the frequency of intravitreal ranibizumab injections than intravitreal ranibizumab monotherapy while maintaining good visual acuity at 6 months., Purpose: To determine the efficacy of the combination therapy of intravitreal ranibizumab (IVR) and 577-nm yellow laser subthreshold micropulse laser photocoagulation (SMLP) for macular edema secondary to branch retinal vein occlusion cystoid macular edema. Methods: Retrospective, consecutive, case–control study. Forty-six eyes of 46 patients with treatment-naive branch retinal vein occlusion cystoid macular edema were enrolled. The IVR + SMLP group consisted of 22 patients who had undergone both SMLP and IVR. Intravitreal ranibizumab group consisted of 24 patients who had undergone IVR monotherapy. Intravitreal ranibizumab therapy was one initial injection and on a pro re nata in both groups, and SMLP was performed at 1 month after IVR in the IVR + SMLP group. Preoperatively and monthly, best-corrected visual acuity and central retinal thickness were evaluated using swept source optical coherence tomography. Results: Best-corrected visual acuity and central retinal thickness significantly improved at 6 months in IVR + SMLP and IVR groups. Best-corrected visual acuity and central retinal thickness were not significantly different between the two groups at any time points. The number of IVR injections during initial 6 months in IVR group (2.3 ± 0.9) was significantly greater (P = 0.034) than that in IVR + SMLP group (1.9 ± 0.8). Conclusion: The combination therapy of IVR and SMLP can treat branch retinal vein occlusion cystoid macular edema effectively, by decreasing the frequency of IVR injections while maintaining good visual acuity.