Red Light-Triggered Anti-Angiogenic and Photodynamic Combination Therapy of Age-Related Macular Degeneration.

Choroidal neovascularization (CNV) is the key pathological event of wet age-related macular degeneration (wAMD) leading to irreversible vision loss. Currently, anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) agents has become the standard treatment for wAMD, while it is still subject to several limitations, including the safety concerns of monthly intravitreal administration and insufficient efficacy for neovascular occlusion. Combined therapy with photodynamic therapy (PDT) and anti-angiogenic agents has emerged as a novel treatment paradigm. Herein, a novel and less-invasive approach is reported to achieve anti-angiogenic and photodynamic combination therapy of wAMD by intravenous administration of a photoactivatable nanosystem (Di-DAS-VER NPs). The nanosystem is self-assembled by reactive oxygen species (ROS)-sensitive dasatinib (DAS) prodrug and photosensitizer verteporfin (VER). After red-light irradiation to the diseased eyes, intraocular release of anti-angiogenic DAS is observed, together with selective neo-vessels occlusion by VER-generated ROS. Notably, Di-DAS-VER NPs demonstrates promising therapeutic efficacy against CNV with minimized systemic toxicity. The study enables an efficient intravenous wAMD therapy by integrating a photoactivation process with combinational therapeutics into one simple nanosystem.

mTOR Signalling Pathway: A Potential Therapeutic Target for Ocular Neurodegenerative Diseases.

Recent advances in the research of the mammalian target of the rapamycin (mTOR) signalling pathway demonstrated that mTOR is a robust therapeutic target for ocular degenerative diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. Although the exact mechanisms of individual ocular degenerative diseases are unclear, they share several common pathological processes, increased and prolonged oxidative stress in particular, which leads to functional and morphological impairment in photoreceptors, retinal ganglion cells (RGCs), or retinal pigment epithelium (RPE). mTOR not only modulates oxidative stress but is also affected by reactive oxygen species (ROS) activation. It is essential to understand the complicated relationship between the mTOR pathway and oxidative stress before its application in the treatment of retinal degeneration. Indeed, the substantial role of mTOR-mediated autophagy in the pathogenies of ocular degenerative diseases should be noted. In reviewing the latest studies, this article summarised the application of rapamycin, an mTOR signalling pathway inhibitor, in different retinal disease models, providing insight into the mechanism of rapamycin in the treatment of retinal neurodegeneration under oxidative stress. Besides basic research, this review also summarised and updated the results of the latest clinical trials of rapamycin in ocular neurodegenerative diseases. In combining the current basic and clinical research results, we provided a more complete picture of mTOR as a potential therapeutic target for ocular neurodegenerative diseases.

Involvement of FSP1-CoQ10-NADH and GSH-GPx-4 pathways in retinal pigment epithelium ferroptosis.

Retinal pigment epithelium (RPE) degeneration plays an important role in a group of retinal disorders such as retinal degeneration (RD) and age-related macular degeneration (AMD). The mechanism of RPE cell death is not yet fully elucidated. Ferroptosis, a novel regulated cell death pathway, participates in cancer and several neurodegenerative diseases. Glutathione peroxidase 4 (GPx-4) and ferroptosis suppressor protein 1 (FSP1) have been proposed to be two main regulators of ferroptosis in these diseases; yet, their roles in RPE degeneration remain elusive. Here, we report that both FSP1-CoQ10-NADH and GSH-GPx-4 pathways inhibit retinal ferroptosis in sodium iodate (SIO)-induced retinal degeneration pathologies in human primary RPE cells (HRPEpiC), ARPE-19 cell line, and mice. GSH-GPx-4 signaling was compromised after a toxic injury caused by SIO, which was aggravated by silencing GPx-4, and ferroptosis inhibitors robustly protected RPE cells from the challenge. Interestingly, while inhibition of FSP1 caused RPE cell death, which was aggravated by SIO exposure, overexpression of FSP1 effectively protected RPE cells from SIO-induced injury, accompanied by a significant down-regulation of CoQ10/NADH and lipid peroxidation. Most importantly, in vivo results showed that Ferrostatin-1 not only remarkably alleviated SIO-induced RPE cell loss, photoreceptor death, and retinal dysfunction but also significantly ameliorated the compromised GSH-GPx-4 and FSP1-CoQ10-NADH signaling in RPE cells isolated from SIO-induced RPE degeneration. These data describe a distinct role for ferroptosis in controlling RPE cell death in vitro and in vivo and may provide a new avenue for identifying treatment targets for RPE degeneration.

Multiple giant retinal tears due to inflicted injury in a neonate.

Purpose: This case represents the longest follow-up period and youngest patient treated for multiple GRTs in the same eye associated with physical abuse. Observations: A 4-week-old otherwise healthy male presented with a constellation of unexplained injuries. Examination of the left eye revealed a mild lens opacity and a shallow retinal detachment with two giant retinal tears (GRTs) and no retinal hemorrhages. Examination of the right eye was unremarkable. Extensive investigations were negative for any underlying medical conditions. The constellation of injuries was felt to be due to physical abuse. The giant retinal tears were treated successfully with lens sparing pars plana vitrectomy. After long-term follow-up of 5 years, there was no cataract progression or development of glaucoma. Conclusions and importance: Clinicians should suspect child abuse in any pediatric patient with GRTs, with or without retinal hemorrhages, to ensure they are connected with the appropriate children's safeguarding society as soon as possible.

Comparison of clinical outcomes of conbercept versus ranibizumab treatment for retinopathy of prematurity: a multicentral prospective randomised controlled trial.

PURPOSE: To compare the recurrence rate and surgical complications of retinopathy of prematurity (ROP) between patients treated with intravitreal injection of conbercept (IVC) and intravitreal injection of ranibizumab (IVR) within 6 months. METHODS: A multicentral prospective, randomised controlled trial was applied from May 2017 to February 2019 for the infants diagnosed as aggressive posterior-ROP, zone I or posterior zone II treatment-requiring ROP by binocular indirect ophthalmoscope and RetCam3. These infants were assigned to randomly receive either intravitreal injection of 0.25 mg conbercept or 0.25 mg ranibizumab. The recurrence rate, fundus fluorescence angiography (FFA) and surgical complications were examined during the follow-up period of 6 months. Recurrent eyes were retreated by laser or another intravitreal injection within the 72 hours. RESULTS: A total of 30 infant patients (60 eyes) underwent IVC and 30 patients (60 eyes) underwent IVR. A total of 10 eyes (16.67%) in the IVC group and 14 eyes (23.34%) in the IVR group developed recurrence. There was no significant statistical difference in the recurrence rate between the two groups (χ2=0.83, p=0.36). The postmenstrual age (PMA) at first injection was (34.60±3.47) weeks in IVC and (35.14±1.76) in IVR group. In recurrent cases, the mean PMA at second treatment were (43.31±3.85) and (43.43±3.89) weeks in the IVC and IVR group, respectively. The period between two treatments was (8.71±6.62) for the IVC and (8.29±2.56) weeks for the IVR group. All these results showed no significant statistical difference between these two groups. The fluorescein leakage were observed in the eyes of recurrent infants by FFA. There were no other complications in the two groups except for complicated cataract in three eyes. CONCLUSION: Both IVC and IVR are effective therapies for the treatment of ROP. Conbercept is a new option for treating ROP.

A prospective randomized clinical trial comparing nepafenac, intravitreal triamcinolone and no adjuvant therapy for epiretinal membrane.

PURPOSE: To compare the efficacy of topical nepafenac 0.1% versus intravitreal triamcinolone acetonide (IVTA) at the conclusion of vitrectomy surgery versus no adjuvant therapy (NAT) in improving macular morphology post-operatively in patients undergoing vitrectomy for epiretinal membrane (ERM), as measured by optical coherence tomography (OCT) imaging and best-corrected visual acuity (BCVA). METHODS: Design: Prospective randomized clinical trial Setting: Multi-centre 80 patients scheduled to undergo vitrectomy surgery for idiopathic ERM were randomized to receive either IVTA (4 mg/0.1 cc) at the end of surgery, topical nepafenac sodium 0.1% TID for 1 month post-operation or no adjuvant treatment (NAT). Optical coherence tomography (OCT) imaging, best-corrected visual acuity and intraocular pressure (IOP) were measured before surgery, and 1 and 2 months post-operation. RESULTS: Although all three groups showed reduction in macular thickness post-operation, the NAT group showed the most improvement, with a reduction of 136.18 ± 29.84 µm at two months. There was no statistically significant difference in macular thickness between the groups at each time point, p = 0.158. The NAT group also had the best recovery in BCVA with an improvement of 0.207 logMAR (10.35 letters) at two months post-operation. There was no statistically significant difference in BCVA between the groups, p = 0.606. There was statistically significant difference in the IOP between the three groups, p = 0.04 only at 1-month visit. The IVTA group had the highest rise in average IOP at both 1 and 2 months post-operation (2.72 and 1.58 mmHg, respectively). CONCLUSION: Our study data suggest there was no advantage in the use of topical nepafenac or IVTA for post-vitrectomy ERM surgery.

Disorganization of the inner retinal layers in diabetic macular edema: systematic review / Desorganização das camadas internas da retina sem edema macular diabético: uma revisão sistemática

ABSTRACT The objective of this article was to review the disorganization of inner retinal layers as a biomarker in diabetic macular edema. A systematic search was conducted in PubMed®/MEDLINE®, Cochrane and Embase until August 2021. The keywords used were: "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" and "biomarkers". No restrictions were imposed on the types of study to be included. The studies selected for eligibility were those that included the diagnosis of diabetic macular edema (center involved, resolved), that were well documented with spectral domain optical coherence tomography, that included disorganization of inner retinal layers as one of the reported alterations, with a follow-up of at least 3 months, and those in which the best corrected visual acuity was evaluated pre and post. There were no limitations regarding the type of treatment established. References of identified studies were searched for additional relevant articles. Articles not published in peer review journals were excluded. All studies were evaluated by two investigators independently. When one of them was in doubt, it was assessed by a third evaluator. A total of seven studies were included. Four were retrospective, longitudinal cohort study and three cross-sectional observational. Regarding the population studied, 61.5% were men and 38.4% were women, most of them had diabetes mellitus type 2 (85.8%). Regarding the stage of diabetes, the percentage of patients with mild nonproliferative diabetic retinopathy was 28.2%, with moderate nonproliferative diabetic retinopathy was 28.5%, with severe nonproliferative diabetic retinopathy was 15.9% and with nonproliferative diabetic retinopathy was 27.4%. In 100% of the studies, the diagnosis of diabetic macular edema in the center involved was included by spectral domain optical coherence tomography (Heidelberg). In all the studies, the presence of disorganization of inner retinal layers was recorded and its association with best corrected visual acuity was evaluated. The measurement was carried out using the LogMAR scale. In all the studies, the presence or absence of disorganization of inner retinal layers was associated with the best corrected worse/better final visual acuity using p <0.05 as a statical significance. The disorganization of inner retinal layers as a biomarker and their presence have shown to be important predictors of visual acuity in the future in patients with diabetic macular edema. Histopathological studies are required to understand its mechanism of action.

RESUMO O objetivo deste artigo foi revisar sobre a desorganização das camadas internas da retina como biomarcador no edema macular diabético. Uma busca sistemática foi realizada no PubMed®/MEDLINE®, Cochrane e Embase até agosto de 2021. As palavras-chave utilizadas foram "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" e "biomarkers". Não foram impostas restrições quanto aos tipos de estudo a serem incluídos. Os estudos selecionados para elegibilidade foram aqueles que incluíram o diagnóstico de edema macular diabético (centro envolvido, resolvido), que foram bem documentados com tomografia de coerência óptica de domínio espectral, que incluíram a desorganização das camadas internas da retina como uma das alterações relatadas, com acompanhamento de pelo menos 3 meses, e aqueles em que a melhor acuidade visual corrigida foi avaliada pré e pós. Não houve limitações quanto ao tipo de tratamento estabelecido. Referências de estudos identificados foram pesquisadas para artigos relevantes adicionais. Foram excluídos os artigos não publicados em revistas de revisão por pares. Todos os estudos foram avaliados por dois investigadores de forma independente. Quando havia dúvida com algum deles, a mesma era avaliada por um terceiro avaliador. Um total de sete estudos foram incluídos. Quatro eram estudos de coorte retrospectivos longitudinais e três eram observacionais transversais. Em relação à população estudada, a proporção de homens foi de 61,5% e de mulheres, 38,4%, a maioria com diabetes mellitus tipo 2 (85,8%). Em relação ao estágio do diabetes, o percentual de pacientes com retinopatia diabética não proliferativa leve foi de 28,2%, retinopatia diabética não proliferativa moderada foi de 28,5%, de retinopatia diabética não proliferativa grave foi de 15,9% e de retinopatia diabética não proliferativa foi de 27,4%. Em 100% dos estudos, o diagnóstico de edema macular diabético no centro envolvido foi incluído pela tomografia de coerência óptica de domínio espectral (Heidelberg). Em todos os estudos, foi registrada a presença de desorganização das camadas internas da retina e avaliada sua associação com a melhor acuidade visual corrigida. A medição foi realizada usando a escala LogMAR. Em todos os estudos, a presença ou ausência de desorganização das camadas internas da retina foi associada a pior/melhor acuidade visual final melhor corrigida usando p<0,05 como significância estática. A desorganização das camadas internas da retina como biomarcador e sua presença têm se mostrado importantes como preditor da acuidade visual no futuro em pacientes com edema macular diabético. Estudos histopatológicos são necessários para entender seu mecanismo de ação.

Cell Ferroptosis: New Mechanism and New Hope for Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a leading cause of inherited retinal degeneration, with more than 60 gene mutations. Despite the genetic heterogenicity, photoreceptor cell damage remains the hallmark of RP pathology. As a result, RP patients usually suffer from reduced night vision, loss of peripheral vision, decreased visual acuity, and impaired color perception. Although photoreceptor cell death is the primary outcome of RP, the underlying mechanisms are not completely elucidated. Ferroptosis is a novel programmed cell death, with characteristic iron overload and lipid peroxidation. Recent studies, using in vitro and in vivo RP models, discovered the involvement of ferroptosis-associated cell death, suggesting a possible new mechanism for RP pathogenesis. In this review, we discuss the association between ferroptosis and photoreceptor cell damage, and its implication in the pathogenesis of RP. We propose that ferroptotic cell death not only opens up a new research area in RP, but may also serve as a novel therapeutic target for RP.

Changes in the Incidence of Retinopathy of Prematurity in Extremely Low Birth Weight Infants in South China From 2004 to 2018.

PURPOSE: To report the changes in incidence and risk factors of retinopathy of prematurity (ROP) in extremely low birth weight (ELBW) infants over a 15-year period in South China. METHODS: The medical records of ELBW infants were retrospectively reviewed through established database of Shenzhen Screening for ROP Cooperative Group. The incidence and severity of ROP were compared among three successive 5-year periods (P1: 2004-2008, P2: 2009-2013, P3: 2014-2018). Gestational age, birth weight, plurality, mode of delivery and gender were analyzed as risk factors for ROP in ELBW infants. RESULTS: Among the 1099 included ELBW infants, 557 (50.7%) had ROP, and 328 (29.9%) had severe ROP. The highest incidence of ROP (87.5%) and severe ROP (82.5%) were seen in P1. From P2 to P3, the incidence of ROP and severe ROP increased from 45.9% to 50.3% for ROP (P < .05) and from 26.4% to 28.3% for severe ROP (P < .05), respectively. Multivariate logistic regression analysis found only gestational age has a significant effect on the incidence of ROP and severe ROP. CONCLUSIONS: From 2004 to 2018, the incidence of ROP and severe ROP in ELBW infants in South China was 50.7% and 29.9%, respectively. Controlling for the other risk factors, only gestational age was statistically associated with ROP in ELBW infants.

Retinal ultra-wide-field colour imaging versus dilated fundus examination to screen for sickle cell retinopathy.

PURPOSE: To compare ultra-wide-field colour fundus imaging (UWFI) to dilated fundus examination (DFE) for the screening of sickle cell retinopathy (SCR). DESIGN: This study is a prospective, blinded, multicentre case series. PARTICIPANTS: This study included two groups: an adult group (n=268 eyes) and a paediatric group (n=168 eyes). Sickle cell disease (SCD) types included haemoglobin S homozygous (HbSS), haemoglobin S and C (HbSC) and Hb S with ß-thalassaemia (HbSß-Thal). METHODS: Participants underwent DFE and UWFI. Each eye received three independent grades (1-4), documented by three graders: clinical grader, image grader 1 and image grader 2. Three clinically relevant diagnostic thresholds were determined. Based on these thresholds, the sensitivity, specificity, positive predictive value and negative predictive value for all three graders were calculated relative to each other as reference tests. RESULTS: HbSC was associated with the most advanced SCR grades. When compared to the clinical grader, image grader 1 and image grader 2 consistently detected more SCR and higher SCR grades in both adult and paediatric groups. In both groups, image grader 1 and image grader 2 identified twice as many cases of capillary occlusion/anastomosis than clinical grader. To detect the presence of any proliferative SCR, image grader 1 and image grader 2 had a sensitivity of 82%, 71% in the paediatrics group and 90% and 72% in the adult group. The clinical grader sensitivity was 52% in the paediatrics group and 53% in the adult group. CONCLUSION: The UWFI is a sensitive tool to screen for SCR. It is superior to DFE in detecting capillary occlusion or anastomosis.

WHO Trial Registration Data Set (TRDS) extension for traditional Chinese medicine 2020: recommendations, explanation, and elaboration.

BACKGROUND: Although the WHO Trial Registration Data Set (TRDS) has been published for many years, the quality of clinical trial registrations with traditional Chinese medicine (TCM) is still not satisfactory, especially about the inadequate reporting on TCM interventions. The development of the WHO TRDS for TCM Extension 2020 (WHO TRDS-TCM 2020) aims to address this inadequacy. METHODS: A group of clinical experts, methodologists, epidemiologists, and editors has developed this WHO TRDS-TCM 2020 through a comprehensive process, including the baseline survey, draft of the initial items, three-round of Delphi survey, solicitation of comments, revision, and finalization. RESULTS: The WHO TRDS-TCM 2020 statement extends the latest version (V.1.3.1) of TRDS published in November 2017. The checklist includes 11 extended items (including subitems), namely Source(s) of Monetary or Material Support (Item 4), Scientific Title (Item 10a and 10b), Countries of Recruitment (Item 11), Health Condition(s) or Problem(s) Studied (Item 12), Intervention(s) (Item 13a, 13b and 13c), Key Inclusion and Exclusion Criteria (Item 14), Primary and Key Secondary Outcomes (Item 19 to 20), and Lay Summary (Item B1). For Item 13 (Interventions), three common TCM interventions--i.e., Chinese herbal medicine formulas, acupuncture and moxibustion-are elaborated. CONCLUSIONS: The group hopes that the WHO TRDS-TCM 2020 can improve the reporting quality and transparency of TCM trial registrations, assist registries in assessing the registration quality of TCM trials, and help readers understand TCM trial design.

A de novo mutation in PITX2 underlies a unique form of Axenfeld-Rieger syndrome with corneal neovascularization and extensive proliferative vitreoretinopathy.

BACKGROUND: Axenfeld-Rieger syndrome is characterized by a spectrum of anterior segment dysgenesis involving neural-crest-derived tissues, most commonly secondary to mutations in the transcription factor genes PITX2 and FOXC1. MATERIALS AND METHODS: Single retrospective case report. RESULTS: A full-term infant presented at 5 weeks of age with bilateral Peters anomaly and Axenfeld-Rieger syndrome, with development of atypical features of progressive corneal neovascularization and proliferative vitreoretinopathy. Despite surgical interventions, the patient progressed to bilateral phthisis bulbi by 22 months of age. Genetic testing revealed a novel de novo p.Leu212Valfs*39 mutation in PITX2, leading to loss of a C-terminal OAR domain that functions in transcriptional regulation. CONCLUSIONS: It is important to consider mutations in PITX2 in atypical cases of anterior segment dysgenesis that also present with abnormalities in the angiogenesis of the anterior and posterior segments.

Comparison of OCT angiography in children with a history of intravitreal injection of ranibizumab versus laser photocoagulation for retinopathy of prematurity.

PURPOSE: To compare the foveal microvascular structure characteristics in children with a history of intravitreal injection of ranibizumab (IVR) versus laser photocoagulation (LP) for retinopathy of prematurity by optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional study, a total of 17 children (28 eyes) underwent IVR and 20 children (37 eyes) underwent LP were recruited. The age of doing OCTA examination of the two groups are 5.4±1.1 years and 6.3±1.8 years, respectively (p=0.07). Spectral-domain OCTA was performed for all the eyes with a scan size of 3×3 mm. The data of the superficial retinal layer were analysed. The foveal avascular zone (FAZ) and vessel density (including vessel length density (VLD) and perfusion density (PD)) were measured using the software of OCTA (Cirrus AngioPlex 5000, Carl Zeiss, Meditec, Dubin, California, USA). The central foveal thicknesses (CFT) were measured by cross-sectional OCT. RESULTS: In the central fovea, the retinal VLD and PD of patients with IVR were 13.82±2.99 mm/mm2 and 0.25±0.05 mm2/mm2, respectively, which were significantly lower than those of the LP group (15.64±2.71 mm/mm2 and 0.28±0.05 mm2/mm2, p=0.01 and p=0.006). The FAZ area of patients with IVR and LP were 0.13±0.09 mm2 and 0.09±0.07 mm2, respectively (p=0.048). The CFT of patients with IVR and LP were 200.7±16.7 µm and 220.9±22.7 µm, respectively (p<0.01). The logarithm of the minimal angle of resolution best-corrected visual acuity of patients with IVR and LP were 0.2±0.1 and 0.1±0.1, respectively (p=0.01). There was no significant difference in the parafoveal and foveal VLD and PD, FAZ morphological index and spherical equivalent refraction (SER) between the two groups. CONCLUSION: The IVR might contribute to microvascular changes in the macular zone, such as reducing the central foveal VLD and PD, while the LP might contribute to microstructural changes, such as smaller FAZ and thicker CFT.

A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome.

An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.

Polypoidal choroidal vasculopathy in Canada.

Polypoidal choroidal vasculopathy (PCV) is an exudative age-related macular degeneration (AMD) subtype found more frequently among Asians than Caucasians. If untreated, it may lead to severe vision loss. PCV appears to be frequently underdiagnosed in Canada, although misdiagnosis of PCV as AMD carries the risk of inadequate treatment and unsatisfactory clinical outcomes. Diagnosis can be made on the basis of multimodal imaging, including optical coherence tomography (OCT) and OCT angiography combined with colour fundus photography, or by other imaging techniques; the gold-standard indocyanine green angiography (ICGA) is not widely used in Canada. Treatment involves anti-vascular endothelial growth factor (anti-VEGF) agents (bevacizumab, ranibizumab, or aflibercept), alone or in combination with photodynamic therapy (PDT). Recent clinical trials have shown that ranibizumab in combination with PDT is superior to ranibizumab monotherapy (EVEREST II), and aflibercept monotherapy is as effective in patients meeting PDT rescue criteria as aflibercept combined with rescue PDT (PLANET). It appears that most Canadian PCV patients are treated with anti-VEGF monotherapy, with or without PDT.

Visual outcomes after treatment in pediatric patients with Coats' disease.

OBJECTIVE: To report visual outcomes for children with Coats' disease after treatment. DESIGN: Retrospective case series. PARTICIPANTS: Pediatric patients with Coats' disease treated between 2000 and 2018 at a tertiary care pediatric hospital. METHODS: Review of medical records. The primary outcome was visual acuity at final follow-up. Anatomical outcomes, retreatment, and risk factors for a poor outcome were also assessed. RESULTS: There were 30 patients with Coats' disease. All cases were unilateral, and 28 (93%) were male. At presentation, 14 (47%) had stage 2 disease (retinal exudates) and 16 (53%) had stage 3 disease (subtotal or total exudative retinal detachment). All patients underwent laser photocoagulation and (or) cryopexy as primary treatment, combined with antivascular endothelial growth factor injection in 7 patients, posterior sclerotomy in 5 patients, and pars plana vitrectomy in 1 patient. Retreatment was required in 16 (53%) patients. After a median follow-up of 3.8 years, visual acuity was 20/50 or better in 6 patients (20%), 20/60 to 20/150 in 3 (10%), 20/200 to counting fingers in 8 (23%), and hand motion or worse in 14 (47%). Greater severity of disease at presentation was significantly associated with a poor visual outcome (p = 0.0001). In terms of complications, 7 (23%) eyes developed cataracts and 2 (7%) progressed to phthisis bulbi, but no patients required enucleation. CONCLUSIONS: The visual prognosis for children with Coats' disease remains poor, particularly in patients with more severe disease at presentation. The risk of severe complications and enucleation is low after treatment.

Long-term visual and anatomic outcomes following early surgery for persistent fetal vasculature: a single-center, 20-year review.

BACKGROUND: Persistent fetal vasculature (PFV) is a spectrum of congenital anomalies caused by complete or partial failure of the ocular fetal vasculature to regress. We report the visual and anatomic outcomes in a large cohort of patients who underwent early surgery for PFV. METHODS: We retrospectively reviewed the medical records of patients who underwent lensectomy and anterior or core vitrectomy for unilateral PFV without primary intraocular lens implantation through limbal or pars plana/plicata approach. Inclusion criteria were surgery prior to 7 months of age, with at least 12 months of follow-up. Eyes with severe posterior segment involvement and retinal detachment deemed beyond repair were excluded. RESULTS: A total of 58 patients met inclusion criteria. Mean age at surgery was 2.1 ± 1.5 months. Mean follow-up was 6.7 ± 4.2 years. At final follow-up, 19 eyes (33%) had visual acuity better than 1.0 logMAR. Thirty-three eyes (57%) developed 1 or more postoperative adverse events: glaucoma in 21 (36%) and retinal detachment in 11 (19%), 8 of which occurred in eyes that had pars plana or pars plicata incisions (P = 0.002). In patients with limbal incisions, 17 of 40 (43%) achieved a visual acuity better than 1.0 logMAR, compared with 2 of 18 patients (11%) with a pars plana/pars plicata incision (P = 0.03). CONCLUSIONS: In our study cohort, early surgery for PFV achieved functional visual acuity in about one-third of patients. Limbal approach to surgery may result in better visual acuity and anatomic results.

Demonstration of anatomical development of the human macula within the first 5 years of life using handheld OCT.

PURPOSE: To demonstrate the anatomical development of the human macula using handheld spectral domain optical coherence tomography (SD-OCT) during the first 5 years of life. METHODS: This study is a cross-sectional, observational case series. Thirty-five normal eyes of 35 full-term/late preterm infants and children under 5 years of age were included. Handheld SD-OCT was used to image the macula of each eye. The data were analyzed using the Duke OCT Retinal Analysis Program v17 software. Retinal thickness maps were generated for the total retinal thickness (TRT), the inner retinal layers thickness (IRL), and the photoreceptor layer thickness (PRL). Based on the early treatment diabetic retinopathy study macular map, average thickness measurements were taken at 4 circles centered on the fovea (diameter): the foveal center (0.5 mm), sector 1 (S1) (1 mm), sector 2 (S2) (3 mm), sector 3 (S3) (6 mm). RESULTS: The median age at participation was 24 months (range 5-52 months). The TRT increased throughout the first 5 years of life, and this increase was statistically significant at the foveal center and S1 (p = 0.01, p = 0.016, respectively). The IRL did not show any significant change in thickness from birth and throughout the first 5 years of life. The PRL thickness showed thickening in the first 24 months of age at the foveal center and S1 which was statistically significant at S1 (p = 0.066, p = 0.016, respectively). Interestingly, this PRL thickness increase plateaus beyond 24 months of age. The photoreceptors inner segment/outer segment (IS/OS) band was identified as a distinct layer in all our subjects. CONCLUSION: Our findings conform with the literature that the anatomical development of the macular IRL completes before 5 months of age and hence before the PRL. We also identify 24 months of age as an important developmental milestone for photoreceptors development in the human macula.