Reperfusion of retinal nonperfusion by neovascular-vascular anastomosis in proliferative diabetic retinopathy.

BACKGROUND: Retinal nonperfusion is a significant cause of vision loss in patients with proliferative diabetic retinopathy (PDR). Therefore, reperfusion of a nonperfusion has been a matter of strong interest, but few previous studies have demonstrated the potential benefits of reperfusion. CASE REPORTS: Here, we report longitudinal optical coherence tomography angiographic analysis of two cases of PDR, in which the retinal neovascularization (RNV) that developed in response to retinal ischemia formed anastomoses with pre-existing physiological retinal vessels, resulting in both superficial and deep capillary reperfusion within the nonperfusion. We named this interesting finding "neovascular-vascular anastomosis." Retinal reperfusion due to neovascular-vascular anastomosis differed from recanalization, defined as reperfusion of once-occluded blood vessels, and has not been reported previously. CONCLUSION: Our observation highlights the potential of RNV to rescue retinal ischemia by the formation of neovascular-vascular anastomoses.

Safety and effectiveness of pre-emptive diabetic vitrectomy in patients with severe, non-fibrotic retinal neovascularisation despite panretinal photocoagulation.

OBJECTIVES: To investigate the safety and effectiveness of pre-emptive vitrectomy in eyes with severe non-fibrotic proliferative diabetic retinopathy. METHODS: A multi-centre, retrospective, observational study. Pre-emptive vitrectomy was performed in non-fibrotic diabetic eyes with a visual acuity (VA) of 20/50 or better, where there was extensive persistent neovascularisation despite prior panretinal photocoagulation, and where the fellow eye had established sight loss despite vitrectomy for tractional complications. The primary outcome measure was the VA at last visit. RESULTS: Twenty patients were included. The mean age was 39 ± 14 years. Fifteen patients were Type 1 diabetic. The median baseline VA was 20/30 and remained stable at 20/28 at last visit (median follow-up period: 24 months). Eight eyes (40.0%) developed post-operative vitreous cavity haemorrhage; 4 of which required a vitreous cavity washout procedure. There were no post-operative retinal detachments. The index eye remained the significantly better eye at all time points bar one month post-surgery. Regression of retinopathy grading was observed in all eyes. CONCLUSION: In this pilot study, we found no sight loss with pre-emptive diabetic vitrectomy. Better eye status was maintained in this high-risk group. Further study with larger number of patients and longer-term follow-up is indicated.

WF SS-OCTA for detecting diabetic retinopathy and evaluating the effect of photocoagulation on posterior vitreous detachment.

Purpose: This study aimed to assess the clinical usefulness of widefield swept source optical coherence tomography angiography (WF SS-OCTA) for detecting microvasculature lesions in diabetic retinopathy (DR) by comparing it with ultra-widefield fluorescein angiography (UWFFA) and to investigate the effect of panretinal photocoagulation (PRP) on posterior vitreous detachment (PVD) status. Methods: Patients with severe non-proliferative DR (NPDR) or proliferative DR (PDR) who were initially treated with PRP were enrolled. They underwent WF SS-OCTA with a 12×12-mm scan pattern of five visual fixations at baseline and at least a 3-month follow-up after PRP treatment. Patients with no contraindications underwent imaging with UWFFA within a week. Images were evaluated using two methods for the areas of the visible field of view (FOV), non-perfusion area (NPA), presence of neovascularization of the disc (NVD), neovascularization elsewhere (NVE), and PVD status. Results: In total, 44 eyes of 28 patients with DR that were initially treated with PRP were analyzed. The FOV of the UWFFA was significantly wider than that of the WF SS-OCTA. The quantitative measurement of the NPAs was consistent between the two methods. NPAs more than 5DA outside the panoramic OCTA imaging area were detected in 1 eye with NPDR (8.3%) and in 10 eyes with PDR (47.8%). WF SS-OCTA had high detection rates for NVDs and NVEs, with a low rate of false positives. After PRP treatment, no eyes indicated progression in the PVD stages around the macula, optical disc, or NVEs at the short follow-up. Conclusion: WF SS-OCTA is clinically useful for evaluating NPAs and neovascularization in DR. PRP treatment does not induce PVD development in the short term.

VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy.

Diabetic retinopathy (DR) is the most common microangiopathic complication of diabetes mellitus, representing a major cause of visual impairment in developed countries. Proliferative DR (PDR) represents the last stage of this extremely complex retinal disease, characterized by the development of neovascularization induced by the abnormal production and release of vascular endothelial growth factor (VEGF). The term VEGF includes different isoforms; VEGF-A represents one of the most important pathogenic factors of DR. Anti-VEGF intravitreal therapies radically changed the outcome of DR, due to combined anti-angiogenic and anti-edematous activities. Nowadays, several anti-VEGF molecules exist, characterized by different pharmacological features and duration. With respect to PDR, although anti-VEGF treatments represented a fundamental step forward in the management of this dramatic complication, a big debate is present in the literature regarding the role of anti-VEGF as substitute of panretinal photocoagulation or if these two approaches may be used in combination. In the present review, we provided an update on VEGF isoforms and their role in DR pathogenesis, on current anti-VEGF molecules and emerging new drugs, and on the current management strategies of PDR. There is an overall agreement regarding the relative advantage provided by anti-VEGF, especially looking at the management of PDR patients requiring vitrectomy, with respect to laser. Based on the current data, laser approaches might be avoided when a perfectly planned anti-VEGF therapeutic strategy can be adopted. Conversely, laser treatment may have a role for those patients unable to guarantee enough compliance to anti-VEGF injections.Key messagesVEGF increased production, stimulated by retinal hypoperfusion and ischaemia, is a major pathogenic factor of neovascular complication onset in diabetic retinopathy and of DR stages progression.Nowadays, several anti-VEGF molecules are available in clinical practice and other molecules are currently under investigation. Each anti-VEGF molecule is characterized by different targets and may interact with multiple biochemical pathways within the eye.All the data agreed in considering anti-VEGF molecules as a first line choice for the management of diabetic retinopathy. Laser treatments may have a role in selected advanced cases and for those patients unable to guarantee enough compliance to intravitreal treatments schemes.

Altered oxylipin levels in human vitreous indicate imbalance in pro-/anti-inflammatory homeostasis in proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR) is an advanced stage of diabetic retinopathy (DR), characterized by retinal neovascularization. It is a progressive fundus disease and a severe complication of diabetes that causes vision impairment. Hyperglycemia-induced persistent low-grade inflammation is a crucial factor underlying the pathogenesis of DR-associated damage and contributing to the progression of PDR. Highly enriched polyunsaturated fatty acids (PUFAs) in the retina are precursors to oxidized metabolites, namely, oxylipins, which exert pro-inflammatory or anti-inflammatory (resolving) effects under different pathological conditions and have been implicated in diabetes. To evaluate differences in oxylipin levels in the vitreous obtained from PDR and non-diabetic subjects, we performed a targeted assessment of oxylipins. A total of 41 patients with PDR and 22 non-diabetic control subjects were enrolled in this study. Vitreous humor obtained during routinely scheduled vitrectomy underwent a targeted but unbiased screening for oxylipins using mass spectrometry-based lipidomics. We found 21 oxylipins showing statistically significant differences in their levels between PDR and non-diabetic subjects (p < 0.05). Lipoxygenase (LOX)- and cytochrome P450 (CYP)- derived oxylipins were the most affected, while cyclooxygenase (COX) oxylipins were affected to a lesser extent. When categorized by their precursor PUFAs, ±19,20-EpDPE, a CYP product of docosahexaenoic acid (DHA) and 12S-HETE, a LOX product of arachidonic acid (ARA), were increased by the largest magnitude. Moreover, of these 21 oxylipins, 7 were considered as potential biomarkers for discriminating PDR patients from the non-diabetic controls. Our results indicate that altered oxylipin levels in the vitreous implicate an underlying imbalanced inflammation-resolution homeostasis in PDR.

Observation of retinal neovascularization using optical coherence tomography angiography after panretinal photocoagulation for proliferative diabetic retinopathy.

BACKGROUND: To describe the longitudinal changes in retinal neovascularization elsewhere (NVE) as observed on optical coherence tomography angiography (OCTA) in proliferative diabetic retinopathy (PDR) treated by panretinal photocoagulation (PRP). METHODS: Each patient included in this prospective clinical study was newly diagnosed with PDR and NVE confirmed by both fundus fluorescein angiography (FFA) and OCTA. They received four sessions of PRP using a multiwavelength laser. Best-corrected visual acuity (BCVA) and OCTA images of the NVE were obtained before each PRP session and at 1 month, 3 months, and 6 months after the PRP treatment. Generalized estimating equations (GEE) was used to investigate the differences between the BCVA and NVE areas before and after PRP. RESULTS: Thirty-two eyes of 32 patients with a mean age of 50.56 ± 7.05 years were included. We found a statistically significant reduction in the NVE area at all time points compared with the baseline except at 6 months (all P < 0.05). Further analysis demonstrated no statistically significant change in the NVE area between two adjacent timepoints except from baseline to post-1st PRP (P < 0.05). BCVA at 3 months showed a statistically significant improvement compared with baseline (P < 0.05), but no significant changes in BCVA were observed during the other visits. CONCLUSIONS: We found an overall regression in the NVE area following PRP starting as early as 1 week after the 1st session and lasting up to 3 months. OCTA provides quantitative information on vascular changes and could be a practical method for the longitudinal evaluation of neovascularization.

Topographical Response of Retinal Neovascularization to Aflibercept or Panretinal Photocoagulation in Proliferative Diabetic Retinopathy: Post Hoc Analysis of the CLARITY Randomized Clinical Trial.

IMPORTANCE: Eyes with proliferative diabetic retinopathy have a variable response to treatment with panretinal photocoagulation (PRP) or anti-vascular endothelial growth factor agents. The location of neovascularization (NV) is associated with outcomes (eg, patients with disc NV [NVD] have poorer visual prognosis than those with NV elsewhere [NVE]). OBJECTIVE: To investigate the distribution of NV in patients with proliferative diabetic retinopathy and the topographical response of NV to treatment with aflibercept or PRP. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the phase 2b randomized clinical single-masked multicenter noninferiority Clinical Efficacy and Mechanistic Evaluation of Aflibercept for Proliferative Diabetic Retinopathy (CLARITY) trial was conducted from November 1, 2019, to September 1, 2020, among 120 treatment-naive patients with proliferative diabetic retinopathy to evaluate the topography of NVD and NVE in 4 quadrants of the retina on color fundus photography at baseline and at 12 and 52 weeks after treatment. EXPOSURES: In the CLARITY trial, patients were randomized to receive intravitreal aflibercept (2 mg/0.05 mL at baseline, 4 weeks, and 8 weeks, and as needed from 12 weeks onward) or PRP (completed in initial fractionated sessions and then on an as-needed basis when reviewed every 8 weeks). MAIN OUTCOMES AND MEASURES: Main outcomes were per-retinal quadrant frequencies of NV at baseline and frequencies of patterns of regression, recurrence, and new occurrence at 12-week and 52-week unmasked follow-up. RESULTS: The study included 120 treatment-naive patients (75 men; mean [SD] age, 54.8 [14.6] years) with proliferative diabetic retinopathy (there was a 1:1 ratio of eyes to patients). At baseline, NVD with or without NVE was observed in 42 eyes (35.0%), and NVE only was found in 78 eyes (65.0%); NVE had a predilection for the nasal quadrant (64 [53.3%]). Rates of regression with treatment were higher among eyes with NVE (89 of 102 [87.3%]) compared with eyes with NVD (23 of 43 [53.5%]) by 52 weeks, with NVD being more resistant to either treatment with higher rates of persistence than NVE (20 of 39 [51.3%] vs 29 of 100 [29.0%]). Considering NVE, the regression rate in the temporal quadrant was lowest (32 of 42 [76.2%]). Eyes treated with aflibercept showed higher rates of regression of NVE compared with those treated with PRP (50 of 52 [96.2%] vs 39 of 50 [78.0%]; difference, 18.2% [95% CI, 5.5%-30.8%]; P = .01), but no difference was found for NVD (11 of 17 [64.7%] vs 12 of 26 [46.2%]; difference, 18.6% [95% CI, -11.2% to 48.3%]; P = .23). CONCLUSIONS AND RELEVANCE: This post hoc analysis found that NVD is less frequent but is associated with more resistance to currently available treatments than NVE. Aflibercept was superior to PRP for treating NVE, but neither treatment was particularly effective against NVD by 52 weeks. Future treatments are needed to better target NVD, which has poorer visual prognosis. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN32207582.

Early pars plana vitrectomy for proliferative diabetic retinopathy: update and review of current literature.

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the leading causes of preventable vision loss in the world and its prevalence continues to increase worldwide. One of the ultimate and visually impairing complications of DR is proliferative diabetic retinopathy (PDR) and subsequent tractional retinal detachment. Treatment modalities, surgical techniques, and a better understanding of the pathophysiology of DR and PDR continue to change the way we approach the disease. The goal of this review is to provide an update on recent treatment modalities and outcomes of proliferative diabetic retinopathy and its complications including tractional retinal detachment. RECENT FINDINGS: Panretinal photocoagulation (PRP), anti-vascular endothelial growth factor (anti-VEGF), and pars plana vitrectomy are the mainstay of PDR treatment. However, PRP and anti-VEGF are associated with significant treatment burden and multiple subsequent treatments. Early vitrectomy is associated with vision preservation, less treatment burden, and less subsequent treatments than therapy with PRP and anti-VEGF. SUMMARY: Concerning costs, high rates of noncompliance in the diabetic population and significant rates of subsequent treatments with initial PRP and anti-VEGF, early vitrectomy for diabetic retinopathy in patients at risk of PDR is a cost-effective long-term stabilizing treatment for diabetics with advanced disease.

RETINAL NEOVASCULARIZATION FROM A PATIENT WITH CUTIS MARMORATA TELANGIECTATICA CONGENITA.

PURPOSE: To report a rare case of peripheral retinal neovascularization in a patient diagnosed with cutis marmorata telangiectatica congenita (CMTC). METHODS: Observational case report. RESULTS: A 16-year-old girl was referred to clinic for retinal evaluation. The patient had a clinical diagnosis of CMTC later confirmed by skin biopsy. Examination revealed temporal peripheral retinal sheathing, as well as lattice degeneration in both eyes. Wide-field fluorescein angiogram showed substantive peripheral retinal nonperfusion with evidence of vascular leakage from areas of presumed retinal neovascularization. The patient subsequently had pan retinal photocoagulation laser treatment to each eye without complication. DISCUSSION: Cutis marmorata telangiectatica congenita is a rare vascular condition known to affect multiple organ systems including the eyes. Although ocular manifestations of CMTC are rare, instances of congenital glaucoma, suprachoroidal hemorrhage, and bilateral total retinal detachments resulting in secondary neovascular glaucoma have been reported. Our patient demonstrates the first reported findings of peripheral nonperfusion and retinal neovascularization related to CMTC in a 16-year-old girl. We propose early retinal examination, wide-field fluorescein angiogram, and early pan retinal photocoagulation laser treatment in patients with peripheral nonperfusion and retinal neovascularization from CMTC.

Chronic myeloid leukaemia accelerates proliferative retinopathy in patients with co-existent diabetes: A risk factor not to be ignored.

OBJECTIVE: To describe the retinal imaging characteristics, retinopathy management strategies and visual outcomes in cases of diabetes with chronic myeloid leukaemia. DESIGN: Retrospective observational study. PARTICIPANTS: Patients with diabetes and chronic myeloid leukaemia managed at our tertiary eye care centre from January 2015 to December 2017. METHODS: Detailed ophthalmic and systemic evaluation, treatment and follow-up records were reviewed. The main measures studied were visual acuity, intra-ocular pressure, retinopathy severity, and surgical indications and techniques. RESULTS: Of the six patients studied, three had diabetes and chronic myeloid leukaemia at presentation, while in three cases chronic myeloid leukaemia was diagnosed following evaluation for proliferative retinopathy. The visual acuity ranged from 20/20 to perception of light. All eyes had marked proliferative retinopathy out of proportion to the exudation. None of the eyes had significant macular oedema. Pan-retinal photocoagulation (10/12, 83.33%), intravitreal anti-vascular endothelial growth factor injection (8/12, 66.67%), vitrectomy (2/12, 16.67%), cataract surgery (2/12, 16.67%) and trabeculectomy followed by cryoablation (2/12, 16.67%) was performed for management of the ocular disease as indicated. Median follow-up was 16.5 months (range: 6-24 months). Final visual acuity ranged from PL to 20/20 with acuity ⩾ 20/100 in eight eyes. Four eyes had advanced optic neuropathy from neovascular glaucoma. CONCLUSION: Accelerated proliferative retinopathy can be seen in cases of diabetes with chronic myeloid leukaemia at the very initial ophthalmic evaluation. Thus, there is a need to alter screening guidelines for retinopathy in cases of diabetes with chronic myeloid leukaemia. Early detection and aggressive management may help preserve visual acuity in such cases.

NOVEL THREE TYPES OF NEOVASCULARIZATION ELSEWHERE DETERMINE THE DIFFERENTIAL CLINICAL FEATURES OF PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To explore the pathological features and clinical significance of three types of neovascularization elsewhere (NVE) in proliferative diabetic retinopathy. METHODS: Neovascularization elsewhere was classified based on the origins and morphologic features using fluorescein angiography and angiographic and structural optical coherence tomography. The topographical distribution, vitreoretinal interface, and responsiveness to panretinal photocoagulation were compared among three types of NVE. RESULTS: One hundred and twenty-seven NVEs were classified into three types. Type 1 NVE was concentrated along or adjacent to vascular arcades; Type 2 was distributed more peripherally than were Types 1 and 3 NVE. The arch bridge-like vitreoretinal interface accounted for 79% of Type 1 NVE. The flat and flat-forward vitreoretinal interface accounted for 95% and 100% in Type 2 and Type 3 NVE, respectively. At 3 months after panretinal photocoagulation, the regression rates for Types 1, 2, and 3 NVE were 82%, 100%, and 80%, respectively. Type 2 NVE showed best regression rate after panretinal photocoagulation (both P < 0.01). CONCLUSION: Three types of NVE determine the distinctly topographical distributions, vitreoretinal interface features, and differential responsiveness to panretinal photocoagulation treatment. This new concept may have important clinical implications in assessing the treatment and prognosis of proliferative diabetic retinopathy.

Predictive values of initial semi-quantitative assessment of relative afferent pupillary defect for neovascularization in central retinal vein occlusion.

PURPOSE: To measure the predictive values of relative afferent pupillary defect (RAPD) assessed semi-quantitatively, and visual acuity (VA) at onset of central retinal vein occlusion (CRVO), for neovascularization. METHODS: Retrospective analysis of the TROXHEMO trial that included patients with CRVO within 30 days after the onset. Inclusion criteria were as follows: semi-quantitative RAPD assessment at diagnosis and/or at one month. RAPD was 'severe' if ≥ 0.9 log. Exclusion criteria were as follows: prophylactic panretinal photocoagulation (PRP) before neovascularization. RESULTS: Among the 119 patients enrolled in the main centre, 101 were analysed. 26 had a neovascular complication during the twelve months of follow-up: rubeosis (19), glaucoma (7) and posterior neovascularization (15). The mean time to onset of a neovascular complication was 4.7 months (1 to 12, median 3 months). All the patients who had a neovascular complication had RAPD at first examination or at one month (negative predictive value (NPV) = 100%) but the positive predictive value (PPV) was low (31%, 95% CI [21%; 42%]). The association 'severe RAPD or VA < 35 letters (ETDRS) at inclusion or at one month' was the best compromise between PPV (53%, [39%; 68%]) and NPV (96%, [92%; 100%]). CONCLUSION: To predict neovascularization, RAPD should be routinely evaluated with filters: the risk of neovascular complication is (a) almost nil if there is no RAPD, (b) very low if there is no severe RAPD and if VA is higher than 35 letters, and (c) higher than 50% if RAPD is ≥ 0.9 log or if VA is less than 35 letters.

Von Hippel-Lindau Syndrome Phenotype With Prominent Vitreoretinal Neovascularization Treated With Early PPV: A Case Series and Literature Review.

BACKGROUND AND OBJECTIVE: To describe a case series of three patients in one family with Von Hippel-Lindau (VHL) disease who presented with vitreoretinal neovascularization and resulting tractional retinal detachments (TRDs). This vitreoretinal phenotype of VHL may benefit from early surgical intervention. PATIENTS AND METHODS: Descriptive case series of three patients in one family with VHL disease. A review of the literature regarding surgical intervention for VHL was performed. RESULTS: All three patients developed prominent intravitreal neovascularization with fibrovascular growth within the vitreous secondary to a retinal capillary hemangioma. Two subjects with intravitreal neovascularization were treated with laser and cryotherapy but eventually developed a TRD. The final vision in these two patients was light perception and 20/300. The eye that was preemptively treated with vitrectomy to remove the vitreous sustaining the neovascularization had visual acuity of 20/50 after surgery. CONCLUSION: Intravitreal neovascularization with fibrovascular proliferation may be an indication for vitrectomy prior to the development of retinal detachment. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:109-115.].

Retinal Nonperfusion in Proliferative Diabetic Retinopathy Before and After Panretinal Photocoagulation Assessed by Widefield OCT Angiography.

PURPOSE: Widefield swept source optical coherence tomography angiography (WF SS-OCTA) imaging was compared with ultra-widefield (UWF) fluorescein angiography (FA) imaging to better understand changes in retinal nonperfusion before and after panretinal photocoagulation (PRP) in treatment-naïve eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational, consecutive case series. METHODS: Participants with treatment-naïve PDR were imaged using the SS-OCTA 12- × 12-mm scan pattern at baseline and at 1 week, 1 month, and 3 months after PRP. UWF FA was obtained at baseline and 3 months after PRP. Selected eyes were imaged using 5 SS-OCTA 12- × 12-mm scans to create a posterior pole montage, and 5 eyes also underwent SS-OCTA imaging at 6 months and 1 year. Areas of retinal nonperfusion (RNP) were drawn independently by 2 masked graders, and analysis of variance (ANOVA) tests were used to compare areas of RNP over time. Main outcome measurements consisted of areas and boundaries of RNP visualized using WF SS-OCTA and UWF FA. RESULTS: From January 2018 through January 2019, WF SS-OCTA was performed on 20 eyes with treatment-naïve PDR from 15 patients. Areas of RNP identified on UWF FA images co-localized with RNP areas visualized on WF SS-OCTA images. There were no statistically significant changes in RNP area on WF SS-OCTA images through 3 months after PRP. Even eyes that were severely ischemic at baseline had no significant changes in RNP area 1 year after PRP. CONCLUSIONS: RNP in PDR can be identified at baseline and imaged serially after PRP using WF SS-OCTA. Retinal perfusion in PDR does not change significantly after PRP. The ability of WF SS-OCTA to longitudinally evaluate RNP areas provides additional justification for adopting WF SS-OCTA as the sole imaging modality for clinical management of PDR.

Peripheral retinal neovascularization secondary to highly myopic superficial Retinoschisis: a case report.

BACKGROUND: Peripheral Retinal neovascularization is well-described as a complication of X-linked retinoschisis, but less often observed in myopic and primary retinoschisis. We present a case of a myopic female who developed retinal microvascular abnormalities due to retinoschisis and subsequent vitreous hemorrhage which would cause severe visual damage without timely and proper treatment. CASE PRESENTATION: A 38-year-old highly myopic Chinese female complained of blurred vision in her right eye. Her best corrected visual acuitiy was 20/20 OU, and her refraction was - 9.00S OU. Dilated fundus examination revealed mild vitreous hemorrhage and abnormal vascular network nasal to the optic disc in her right eye. Optical Coherence Tomography (OCT)- angiography (OCTA) B-Scan showed superficial retinoschisis and well-depicted abnormal retinal microvascular network in inner retinal layer. Sectoral scatter laser photocoagulation was administered. Regression of most abnormal vessels was achieved in 1 month, but the patient experienced an unexpected episode of vitreous hemorrhage 3 months after the initial treatment, which was absorbed spontaneously in 2 weeks. Supplemental laser photocoagulation was applied and regular follow-up visit was suggested. CONCLUSION: Superficial retinoschisis in pathological myopia can be a driver of retinal microvascular abnormalities, possibly neovascularization, an extremely rare but severe complication which can be vision-threatening without timely and proper intervention.

Comparison of the Efficacy Between Intravitreal Aflibercept and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity.

PURPOSE: To compare the efficacy of intravitreal aflibercept and laser photocoagulation in the treatment of retinopathy of prematurity (ROP). METHODS: The files of patients who were diagnosed as having type 1 ROP or aggressive posterior ROP (APROP) and treated with laser photocoagulation and 1 mg/0.025 mL of intravitreal aflibercept were retrospectively analyzed. The patients' birth weight, gestational age, detection week of the disease, zone, stage, presence of plus disease and rubeosis, regression of ROP, re-treatments administered during the follow-up, and spherical equivalent values obtained at the corrected sixth month were recorded. RESULTS: The study included 27 eyes of 15 patients who underwent laser photocoagulation and 24 eyes of 12 patients who received intravitreal aflibercept. Retinal vascularization was in zone II in all eyes in the laser photocoagulation group and zone 1 in 22 eyes (91.7%) in the intravitreal aflibercept group (P < .05). In the laser photocoagulation group, 25 eyes (92.6%) had stage 3 ROP and 2 eyes (7.4%) had stage 2 ROP. In the intravitreal aflibercept group, 14 eyes (58.3%) had stage 3 ROP and 10 eyes (41.7%) had APROP (P < .05). Treatment was established at a postmenstrual age of 37.6 ± 2.5 weeks in the laser photocoagulation group and 34.2 ± 2.4 weeks in the intravitreal aflibercept group (P < .05). The regression rates after treatment were 92.6% and 100%, respectively (P > .05). In the intravitreal aflibercept group, laser photocoagulation was performed on 10 eyes (41.6%) during follow-up visits. Spherical equivalents were measured as +1.10 ± 2.30 and +1.50 ± 2.41 diopters, respectively (P < .05) at the corrected sixth month. CONCLUSIONS: Intravitreal aflibercept is an effective treatment for ROP. However, it requires more additional treatments than laser photocoagulation during the follow-up visits. [J Pediatr Ophthalmol Strabismus. 2020;57(1):54-60.].

Combined Vitrectomy and Anti-VEGF Treatment for Stage 4 Retinopathy of Prematurity With Extensive Neovascular Proliferation.

PURPOSE: To study the role of combined vitrectomy and intravitreal anti-vascular endothelial growth factor (VEGF) injection for stage 4 retinopathy of prematurity (ROP) with extensive neovascular proliferation. METHODS: In a retrospective interventional study at a tertiary eye care center, 15 eyes (9 infants) with advanced stage 4 ROP underwent 25-gauge vitrectomy combined with intravitreal 0.625 mg of bevacizumab (n = 12) or 0.25 mg of ranibizumab (n = 3) injection and were followed up until 65 weeks' postconceptional age (PCA). The perinatal history, tractional retinal detachment (TRD) characteristics (zone, stage, and presence of "plus" disease), treatment details, and anatomical outcomes were reviewed. The main outcome measures were fibrovascular tissue and TRD regression and final macular status. RESULTS: Mean gestational age and birth weight were 28.5 ± 1.2 weeks and 1,167 ± 185 g, respectively. Thirteen eyes had zone I disease and 2 eyes had zone II disease. Thirteen eyes were stage 4A and 2 eyes were stage 4B ROP. The morphology was aggressive posterior ROP in 10 eyes. The mean PCA at surgery was 37.8 ± 2.3 weeks. Lensectomy was also performed in 2 eyes. Rapid fibrovascular tissue regression was seen in 14 eyes within 2 weeks, followed by TRD regression and macular vascularization, although 2 eyes had macular pucker formation. Persistent vitreous bleeding was present in 1 eye, which needed lavage, and eventually the TRD regressed. Disease reactivation was noted in 1 eye at 5 weeks and was managed with repeat intravitreal anti-VEGF injection. CONCLUSIONS: Anti-VEGF treatment combined with vitrectomy leads to rapid disease regression in advanced stage 4 ROP with extensive neovascular proliferation. [J Pediatr Ophthalmol Strabismus. 2020;57(1):61-66.].

Zone of retinal vascularization and refractive error in premature eyes with and without spontaneously regressed retinopathy of prematurity.

PURPOSE: To evaluate the relationship between zone of retinal vascularization and refractive error in premature infants without retinopathy of prematurity (ROP) or with spontaneously regressed ROP. METHODS: The medical records of neonates screened for ROP between 2009 and 2015 at a tertiary academic center were reviewed retrospectively. Cases included untreated eyes with spontaneously regressed ROP; premature eyes without a diagnosis of ROP were control subjects. Primary outcomes were zone of retinal vascularization and refractive error, determined by cycloplegic retinoscopy (CR). RESULTS: Of 378 eyes evaluated, 184 had ROP, 24 of which underwent treatment and were excluded. Mean corrected age at first CR was 7.5 months. Seventeen eyes without ROP were myopic at first CR (8.8%), compared to 35 eyes with regressed ROP (21.9%). No untreated eyes had halted vasculature in zone I; notably, 44% of spontaneously regressed zone II eyes were myopic. Irrespective of ROP status, CR significantly differed by zone of vascularization (P < 0.001), with more myopia occurring with posterior halting of vascularization. For all eyes, CR significantly differed between complete vascularization versus zone II (P < 0.0001) and zone III versus zone II (P = 0.001); zone III versus complete vascularization did not statistically differ (P = 0.15). This relationship held true for untreated, spontaneously regressed ROP eyes (P < 0.01, P = 0.01, P = 0.8343). CONCLUSIONS: More myopic refraction occurred in neonates screened for ROP with posterior halting of vascularization. Patients with halted vascular growth in zone II should be closely monitored for myopia and refractive amblyopia.

Peripheral Microvascular Abnormalities Detected by Wide-Field Fluorescein Angiography in Eyes with Branch Retinal Vein Occlusion.

PURPOSE: To evaluate the location of microvascular abnormalities using wide-field fluorescein angiography (WFFA) and investigate the impact on visual outcome in eyes with branch retinal vein occlusion (BRVO). METHODS: Forty eyes of 39 patients (24 males and 15 females with an average age of 71 years) were retrospectively reviewed. One patient had BRVO bilaterally. WFFA was performed in all patients to evaluate perfusion status and detect microvascular abnormalities. The WFFA images were divided into 3 zones: zone 1, posterior pole; zone 2, mid-periphery; zone 3, far periphery, in order to document the presence of microvascular abnormalities. Scatter retinal photocoagulation (PC) was performed for retinal neovascularization (NV) and/or widespread nonperfused areas (NPAs). RESULTS: The incidence of microvascular abnormalities in zone 3 was significantly (p < 0.0001) less than in zones 1 and 2. The presence of larger NPAs in zone 1, but not in zone 3, was associated with the incidence of NV and vitreous hemorrhage. The presence of peripheral lesions and the application of PC did not affect the visual outcome. CONCLUSION: The presence of peripheral abnormalities or scatter PC for NPAs did not affect the visual outcome in eyes with BRVO.