Comparing Half-Dose Photodynamic Therapy with Subthreshold Micropulse Laser for the Treatment of Central Serous Chorioretinopathy.

PURPOSE: To compare the anatomic and functional outcomes of half-dose photodynamic therapy (PDT) and yellow 577-nm subthreshold micropulse laser (SMLT) in treating patients with chronic central serous chorioretinopathy (CSCR). DESIGN: Prospective, double-masked, randomized, controlled clinical trial. PARTICIPANTS: Patients with chronic CSCR confirmed by clinical features and multimodal imaging. METHODS: Eligible patients were randomized (1:1) to receive half-dose PDT or SMLT. The same treatment was repeated if persistent subretinal fluid (SRF) was observed. Treatment responses were evaluated 1 month after treatment and every 3 months until the end point at 12 months. MAIN OUTCOME MEASURES: The primary outcome measure was the complete resolution of SRF on OCT scan at month 12. Secondary outcomes included the changes in best-corrected visual acuity (BCVA), central macular thickness (CMT) as measured by OCT, retinal sensitivity as measured by microperimetry, and vision-related quality of life using the National Eye Institute 25-Item Visual Function Questionnaire. RESULTS: Between April 2017 and October 2020, 68 patients were recruited. At 1 month after treatment, SRF resolved in 8 (24.2%) of 33 patients receiving SMLT and in 20 (58.8%) of 34 patients receiving half-dose PDT. This increased to 23 (82.1%) of 28 patients in the SMLT group and 30 (90.9%) of 33 patients in the half-dose PDT group at 12 months of follow-up. Kaplan-Meier survival curves showed significantly faster resolution of SRF in the half-dose PDT group than the SMLT group (P = 0.016). Both groups showed significant improvement in BCVA (-0.12 ± 0.21, P = 0.005 for SMLT; -0.13 ± 0.12, P < 0.001 for half-dose PDT), CMT (-154.2 ± 105.6, P < 0.001 for SMLT; -140.8 ± 94.0, P < 0.001 for half-dose PDT), and retinal sensitivity (5.70 ± 5.02, P < 0.001 for SMLT; 6.05 ± 3.83, P < 0.001 for half-dose PDT) at 12 months compared with baseline. There was no significant difference between the 2 treatment groups at each time point in all investigations except BCVA at 3 months (P = 0.03). CONCLUSIONS: When comparing half-dose PDT to subthreshold SMLT, this study has shown both treatments to be viable options, with half-dose PDT achieving faster anatomic success and functional improvement. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Multi-Polymorphism Analysis Reveals Joint Effects in Males With Chronic Central Serous Chorioretinopathy.

Purpose: Central serous chorioretinopathy (CSCR) is a leading cause of central vision impairment in the working-age population with male predilection. Knowledge about the genetic basis of CSCR and its male predilection remained limited. This study aimed to evaluate the association patterns of multiple gene variants in chronic CSCR (cCSCR) in Chinese patients. Methods: This case-control genetic association study included 531 patients with cCSCR and 2383 controls from two independent Chinese cohorts. Nine single-nucleotide polymorphisms (SNPs) of six genes, namely CFH, NR3C2, GATA5, VIPR2, TNFRSF10A, and ARMS2, were genotyped in all subjects. The main outcome measures were the association of individual single-nucleotide polymorphism (SNP) with cCSCR, the sex-stratification effects of individual SNP, and joint effects of different SNPs on cCSCR. Results: Association results in the two cohorts were consistent with low heterogeneities. In the combined analysis, SNPs CFH rs800292 (odds ratio [OR] = 1.25, P = 0.0020), CFH rs1329428 (OR = 1.23, P = 0.0037), and TNFRSF10A rs13278062 (OR = 1.43, P = 0.0014) were significantly associated with cCSCR. In stratification analysis by sex, 3 SNPs in CFH, rs3753394, rs800292, and rs1329428, were associated with cCSCR in male patients, but not in female patients. Joint analysis revealed that subjects homozygous for the risk alleles of CFH rs800292 and TNFRSF10A rs13278062 had over 4-fold of increased risk of cCSCR when compared with subjects homozygous for the non-risk alleles (OR = 4.06, P = 2.30 × 10-5). Conclusions: This study revealed main and joint effects of SNPs in CFH and TNFRSF10A on cCSCR, and suggested CFH as a potential genetic factor underlying the male predilection of cCSCR. Further replication in other study populations is needed.

Myopic macular diseases: A review.

Recent evidence has demonstrated that the global public health burden of myopia is rising rapidly. Highly myopic eyes are associated with increased frequency of eye disorders that can lead to irreversible visual impairment. With recent technological advancement in ophthalmic imaging modalities, various macular complications associated with pathologic myopia are being elucidated. The development and progression of myopic chorioretinal atrophy, myopic macular neovascularization, myopic traction maculopathy and dome-shaped macula are vision-threatening myopic macular diseases. In order to overcome the challenges in managing patients with pathologic myopia, it is important to have a complete understanding in the natural course of these myopic macular diseases. Standardising the classification criteria of pathologic myopia is essential for enhancing clinical surveillance. Personalised pharmaceutical therapy and surgical interventions will help to optimise the treatment outcomes in patients suffering from these myopic macular diseases.

Oculoplastic surgical simulation using goat sockets.

PURPOSE: To describe a reproducible and easily available goat socket model for training of various oculoplastic operations, and to evaluate trainees' perception of this training model in terms of their learning progress and satisfaction. METHODS: Goat sockets including orbital rim and eye with eyelids were harvested in form of a split-head model. Ophthalmology residents underwent individual surgical training using the goat socket model, supervised by an oculoplastic attending. Participants completed a questionnaire in form of a 5-point Likert Scale to evaluate their learning progress and satisfaction. OUTCOME MEASURES: Types of oculoplastic operations performed using the goat socket models, and participants' rating of their learning progress and satisfaction were reported. RESULTS: A wide range of oculoplastic operations including both eyelid and orbital operations could be simulated because of similarities of the goat eye model to the human eye anatomy. Fifteen ophthalmic trainees participated in surgical training using the goat eye model. All (100%) participants agreed that surgical simulation using the goat socket model increased their skills in surgical instrumentation and carrying out surgical steps, and their confidence in operating on patients. Most (87%) agreed the model resembled reasonably well compared to surgeries in human, and 93% would recommend training with the model to fellow resident ophthalmologists before operating on human patients. CONCLUSIONS: Oculoplastic surgical training using goat sockets is simple, readily available, and inexpensive. Trainee users showed promising feedback and positive learning progress using the goat socket model.

Safety review of anti-VEGF therapy in patients with myopic choroidal neovascularization.

INTRODUCTION: Anti-angiogenesis therapy with intravitreal anti-VEGF agents is now the standard-of-care treatment for myopic choroidal neovascularization (CNV). AREAS COVERED: We provide a critical review of the safety of all the anti-VEGF agents currently used for treating myopic CNV including ranibizumab, aflibercept, conbercept, bevacizumab, and ziv-aflibercept. EXPERT OPINION: Anti-VEGF therapy for myopic CNV with the currently available anti-VEGF drugs generally have favorable safety outcomes in the short-term. Nonetheless, ocular adverse events following anti-VEGF therapy for myopic CNV may develop and these include worsening or new development of myopic traction maculopathy, increased risk of retinal detachment, and progression of chorioretinal atrophy. Clinicians should be aware of these potential complications and evaluate them before and after anti-VEGF therapy.

Fundus Autofluorescence and Optical Coherence Tomography Characteristics in Different Stages of Central Serous Chorioretinopathy.

OBJECTIVE: To describe the morphological changes on fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) imaging at different chronicity of central serous chorioretinopathy (CSC). METHODS: This cross-sectional study included patients with CSC of different chronicity. Changes in FAF scans and morphological changes on SD-OCT were evaluated and compared at different stages of CSC. RESULTS: Sixty-nine patients were enrolled in the study, with a mean age of 52.1 ± 11.8 years. A distinct hypoautofluorescence (AF) pattern was observed at the leakage point in acute CSC (100%). The leakage site was indistinguishable in 48% of the patients with late-chronic CSC. The majority of acute CSC patients showed hyper-AF in the area of serous retinal detachment (SRD), which persisted in the early-chronic stage of CSC. In late-chronic CSC, many cases of hypo-AF (22.2%) and mixed-pattern AF (14.8%) were observed. SD-OCT revealed evolving features of retinal pigment epithelium (RPE) abnormalities in a time-dependent manner: from peaked PEDs in acute CSC to low-lying PEDs in early-chronic CSC and, eventually, flat, irregular PEDs in late-chronic CSC. The average thickness of the photoreceptor layer (inner and outer segment; IS/OS) was 79 µm in the acute group and 55.2 µm in the chronic group. The photoreceptor layer (IS/OS) height was positively associated with visual acuity (p=0.002). CONCLUSION: Different stages of CSC present different patterns on FAF and SD-OCT imaging. Chronicity of CSC can be estimated using specific features in these images. Photoreceptor layer (IS/OS) height acts as a good and objective predictor of visual outcomes in CSC patients.

Ranibizumab for myopic choroidal neovascularization.

INTRODUCTION: Myopic choroidal neovascularization (CNV) is one of the most vision-threatening complications in patients with pathologic myopia. Over the last decade, anti-angiogenesis therapy with anti-vascular endothelial growth factor (anti-VEGF) agents has become the standard-of-care treatment for myopic CNV and ranibizumab has been approved for treating myopic CNV. AREAS COVERED: Review of preclinical studies and clinical trials data supporting the use of ranibizumab for myopic CNV. Discussion on the mechanisms, efficacy, safety, regulatory affairs, and future directions of ranibizumab for myopic CNV are highlighted. EXPERT OPINION: Ranibizumab has demonstrated good efficacy and safety profile in multiple clinical trials and long-term studies for treating myopic CNV. Cost-effective analysis has shown that ranibizumab therapy is a cost-effective treatment for myopic CNV. Among the currently available anti-VEGF agents, ranibizumab is the only drug that is approved for the treatment of myopic CNV by the US Food and Drug Administration. In the coming few years, biosimilars of ranibizumab may become available and will have the potential to lower the cost of ranibizumab. Long-term visual gain after ranibizumab treatment for myopic CNV is limited by chorioretinal atrophy associated with pathologic myopia and further research is required to tackle the development of chorioretinal atrophy.

High prevalence of myopia in children and their parents in Hong Kong Chinese Population: the Hong Kong Children Eye Study.

PURPOSE: To determine the myopia prevalence in Hong Kong Chinese children and their parents. METHODS: It was a population-based cross-sectional study. A total of 4257 children aged 6-8 years, and 5880 parents were recruited in the Hong Kong Children Eye Study. Cycloplegic autorefraction was measured for children; and non-cycloplegic autorefraction for parents. Parental educational level, children's outdoor time, and near work were collected by validated questionnaires. RESULTS: In children aged 6-8 years, 25.0% were myopic, and among them, 12.7% for the 6-year-olds, 24.4% for the 7-year-olds and 36.1% for the 8-year-old. About 0.7% of children aged 8 years were high myopia. In all age groups, boys (their myopia rate: 13.9% at 6 years, 26.7% at 7 years, and 38.3% at 8 years) were more myopic than girls (11.3% at 6 years, 22.0% at 7 years, 33.4% at 8 years). Among parents, 72.2% were myopic (mother, 73.2%; father, 70.7%) and 13.5% high myopia (mother, 12.8%; father, 14.5%). It was observed that prevalence decreased with ages and increased with education level. CONCLUSION: There is a strikingly high prevalence of myopia in Hong Kong children aged 6-8, much higher than that of other regions of China. Of note, the prevalence of children was similar to that in 15 years ago. Furthermore, the myopia prevalence of parents is high, and it had already increased in this cohort. Prevention of childhood myopia is important, likewise for visual complications from high myopia in adults.

Choroidal thickness in thyroid-associated orbitopathy.

IMPORTANCE: To investigate the choroidal thickness (CT) in patients with thyroid-associated orbitopathy (TAO). BACKGROUND: To compare CT of TAO patients and healthy subjects. DESIGN: Prospective cross-sectional study in a public hospital. PARTICIPANTS: One hundred and four eyes of 52 TAO patients and 52 eyes of 26 healthy subjects. METHODS: CT was measured with enhanced-depth imaging optical coherence tomography (EDI-OCT) at the subfoveal, macular and peripapillary regions. Multivariate linear regression was used to evaluate the associations of subfoveal CT with systemic and ocular variables among TAO eyes. MAIN OUTCOME MEASURES: CT of both groups. RESULTS: CT of eyes with TAO was significantly increased at the subfoveal region, 1 and 2 mm from the fovea nasally, temporally and superiorly, and 1 mm inferior to the fovea (all P < .05). No significant difference was found in CT at 2 mm inferior to the fovea (P = .094) and all four quadrants of the peripapillary region (superior, P = .096; nasal, P = .732; inferior, P = .179; temporal, P = .052). Among TAO eyes, thinner subfoveal choroid was associated with worsening exophthalmos (P = .043), poorer visual acuity (P = .017), increasing age (P = .040) and axial length (P < .001). There was no association between CT and clinical activity score (P = .239). CONCLUSIONS AND RELEVANCE: TAO patients showed thicker choroid than controls over the macula, but not the peripapillary regions. Thinner subfoveal choroid was associated with worsening exophthalmos and poorer vision. EDI-OCT can monitor choroidal vascular changes associated with TAO and its complications.

Anti-Vascular Endothelial Growth Factor Therapy for Myopic Choroidal Neovascularization.

Myopic choroidal neovascularization (CNV) is one of the most vision-impairing complications in patients with pathologic myopia. It is also one of the most frequently encountered non.age-related macular degeneration causes of CNV and affects young patients in the working age group. Fluorescein angiography (FA) and spectral domain optical coherence tomography (OCT) are generally indicated to confirm the diagnosis of active myopic CNV before initiation of treatment. Without treatment, natural history studies have shown that the vision outcome can be very poor. More recently, a number of retrospective, prospective and phase 3, multicenter, randomized controlled trials have established the safety and efficacy of intravitreal anti.vascular endothelial growth factor (VEGF) agents for the treatment of myopic CNV. Long-term follow-up studies have found that some of the initial vision gained after intravitreal anti-VEGF therapy may not be maintained, owing to the presence and progression of chorioretinal atrophy (CRA) adjacent to the CNV. Further research on clinical and imaging characteristics may elucidate the prognostic factors that are crucial to optimizing the treatment and prevention of visual impairment associated with myopic CNV.

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations.

Purpose: We determine the angiopoietin 2 (ANGPT2) gene as a new susceptibility gene for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). Methods: A total of 34 haplotype-tagging single-nucleotide polymorphisms (SNPs) were first genotyped in an exploratory Hong Kong Chinese cohort. Suggestive SNPs were replicated in a Shantou Chinese cohort and an Osaka Japanese cohort, with a total of 2343 subjects. The SNP rs800292 in the complement factor H (CFH) gene was genotyped in all the subjects. Genetic association and gene-gene interaction were analyzed. Results: In the Hong Kong cohort, four SNPs in ANGPT2 (rs13255574, rs4455855, rs13269021, and rs11775442) were nominally associated with nAMD and PCV. The four ANGPT2 SNPs showed the same trends of association in the Shantou and Osaka cohorts. Combining the data from the 3 study cohorts revealed that SNPs rs4455855 and rs13269021 achieved study-wise significance (P < 0.0016), conferring an approximately 1.3-fold of increased risk for nAMD and PCV. Interaction analysis revealed the CFH SNP rs800292 has a highly significant interaction with the ANGPT2 SNP rs13269021 in nAMD and PCV in the combined analysis. Subsequent stratification analysis confirmed the interaction. Conclusions: This study reveals ANGPT2 as a new susceptibility gene for nAMD and PCV, and it may affect disease susceptibility in association with CFH. Thus, this report provides new insights into the genetic architecture of nAMD and PCV.

RISK FACTORS FOR DEVELOPMENT OF MACULAR HOLE RETINAL DETACHMENT AFTER PARS PLANA VITRECTOMY FOR PATHOLOGIC MYOPIC FOVEOSCHISIS.

PURPOSE: To identify the risk factors for the development of macular hole retinal detachment (MHRD) after vitrectomy without internal limiting membrane peeling for pathologic MF. METHODS: We retrospectively reviewed the records of 131 eyes (115 patients) treated with vitrectomy for pathologic MF from 2009 to 2014. The best-corrected visual acuity (BCVA), refractive error, axial length, and spectral-domain optical coherence tomography findings were analyzed. RESULTS: Postoperative MHRD developed in 7 eyes (5.3%). Between patients with or without secondary MHRD after vitrectomy, there were no significant differences in age, sex, axial length, preoperative BCVA, refractive error, lens status, and presence of posterior staphyloma. Spectral-domain optical coherence tomography showed all 7 eyes (100%) had foveal detachment, while only 47 patients (37.9%) of 124 eyes had foveal detachment (P = 0.004). There was no significant difference between preoperative and postoperative BCVA in the 7 eyes with MHRD. The postoperative BCVA in the 124 eyes without MHRD was significantly improved (P < 0.001). Among the 124 eyes, both preoperative and postoperative BCVA of eyes with foveal detachment was worse than the eyes without foveal detachment (P < 0.001, respectively). CONCLUSION: Preoperative foveal detachment is a risk factor for the development of MHRD after vitrectomy for pathologic MF.

Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis.

The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed.

Genetics of Bietti Crystalline Dystrophy.

Bietti crystalline dystrophy (BCD) is an inherited retinal degenerative disease characterized by crystalline deposits in the retina, followed by progressive atrophy of the retinal pigment epithelium (RPE), choriocapillaris, and photoreceptors. CYP4V2 has been identified as the causative gene for BCD. The CYP4V2 gene belongs to the cytochrome P450 superfamily and encodes for fatty acid ω-hydroxylase of both saturated and unsaturated fatty acids. The CYP4V2 protein is localized most abundantly within the endoplasmic reticulum in the RPE and is postulated to play a role in the physiological lipid recycling system between the RPE and photoreceptors to maintain visual function. Electroretinographic assessments have revealed progressive dysfunction of rod and cone photoreceptors in patients with BCD. Several genotypes have been associated with more severe phenotypes based on clinical and electrophysiological findings. With the advent of multimodal imaging with spectral domain optical coherence tomography, fundus autofluorescence, and adaptive optics scanning laser ophthalmoscopy, more precise delineation of BCD severity and progression is now possible, allowing for the potential future development of targets for gene therapy.