RETINAL VEIN OCCLUSIONS, FROM BASICS TO THE LATEST TREATMENT.

PURPOSE: To review the pathophysiology, diagnosis, and updated treatments of retinal vein occlusions (RVOs). METHODS: A review of the literature was performed, focusing on the epidemiology, pathophysiology, diagnosis, and treatments (including both medical and surgical treatments) of RVO. Based on this review, a comprehensive overview was provided regarding the topic of RVO and focused on recent treatment updates. RESULTS: Retinal vein occlusions have an age- and sex-standardized prevalence of 5.20 per 1,000 for any RVO, 4.42 per 1,000 for branch RVO, 0.80 per 1,000 for central RVO. Worldwide, an estimated 16.4 million adults are affected by RVOs, with 2.5 million affected by central RVO and 13.9 million affected by branch RVO. Retinal vein occlusion is recognized as an important cause of blindness and the diagnostic approaches and treatment options for RVO are reviewed and reported. The current treatment options including medical treatments (bevacizumab, ranibizumab, aflibercept, triamcinolone, and dexamethasone implants) and surgical alternatives were reviewed and reported with summaries on the corresponding strength of evidence. CONCLUSION: Despite the understanding of this disease entity, challenges persist in the long-term treatment of RVO-related complications and visual loss. This review provided a detailed summary on the rationality and efficacy of recently developed treatment regimes and evaluated the potential benefit of combination therapy.

Genes in the high-density lipoprotein metabolic pathway in age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To investigate the associations of genetic variants in the high-density lipoprotein (HDL) metabolism pathway with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). DESIGN: Cross-sectional, case-control association study. PARTICIPANTS: A Chinese case-control group of 200 neovascular AMD patients, 233 PCV patients, and 275 control subjects. METHODS: Eight single nucleotide polymorphisms (SNPs) from 6 genes of the HDL metabolism pathway and 2 known AMD-associated SNPs, rs800292 (from complement factor H [CFH]) and rs11200638 (from HtrA serine peptidase 1 [HTRA1]), were genotyped in all study subjects using the TaqMan genotyping technology (Applied Biosystems, Foster City, CA). MAIN OUTCOME MEASURES: Allele and genotypic frequencies of selected SNPs. RESULTS: The SNP rs3764261 in the cholesteryl ester transfer protein (CETP) gene was associated significantly with neovascular AMD (P = 1.82×10(-4); odds ratio [OR], 1.89) and PCV (P = 4.04×10(-4); OR, 1.80). The associations remained significant after adjusting for the CFH SNP rs800292 and the HTRA1 SNP rs11200638. A significant interaction between the CETP SNP rs3764261 and the CFH SNP rs800292 existed in both neovascular AMD and PCV, the rs800292 G allele conferring a significantly increased risk of the diseases only in individuals carrying the risk allele T of rs3764261. A borderline association was detected between the ATP-binding cassette, subfamily G, member 1 (ABCG1) gene SNP rs57137919 and PCV (P = 0.03). CONCLUSIONS: Our results showed that CETP is a susceptibility gene for neovascular AMD and PCV and that ABCG1 a putative gene for PCV. CETP exerts a modifying effect on CFH in the genetic risk. Our data suggest a link of the HDL metabolism pathway with neovascular AMD and PCV.

Management of Choroidal Neovascularization Secondary to Pathological Myopia: The Era of Changes.

Choroidal neovascularization (CNV) secondary to pathological myopia is an important cause of significant visual impairment in young adults. High myopia is particularly prevalent in Asian population. New scientific contributions have been made to the understanding of high myopia and myopic CNV. Treatment for myopic CNV has previously relied on photodynamic therapy, laser photocoagulation, and submacular surgery. The treatment outcomes from these modalities are, however, controversial. The introduction of antiangiogenic agents including bevacizumab and ranibizumab has brought the treatment of myopic CNV into a new era. The purpose of this review was to provide an overview of the natural history of myopic CNV, the prognostic factors, and the various treatment options including laser photocoagulation and photodynamic therapy, with particular attention on antiangiogenic agents.

Prevalence and risk factors of posterior vitreous detachment in a Chinese adult population: the Handan eye study.

BACKGROUND: To describe the prevalence and associations of posterior vitreous detachment (PVD) in a rural adult Chinese population. METHODS: All eligible subjects were requested to carry out a comprehensive eye examination; PVD was a pre-specified outcome variable and was determined via biomicroscopical examination (slit-lamp biomicroscopy) with a +90-D preset lens after mydriasis. Prevalence was standardized to China population census (2000). RESULTS: 5890 (86.2%) subjects completed the examination of slit-lamp biomicroscopy with a +90-D lens. PVD was present in 160 participants (2.7%); the standardized prevalence was 2.0% (95% confidence interval [CI], 1.6-2.3%). PVD developed increasingly with age (P for trend < 0.001) for both men and women. Using a multivariate regression model, older people were found to run a higher risk of developing PVD than younger people, and women were found to have a higher risk than men (OR, 2.9; 95% CI, 1.5-5.9). Diabetes, hypertension, smoking, drinking, and intraocular pressure (IOP) were not significantly associated with PVD. CONCLUSIONS: About one in fifty people is found to have PVD in this population-based study. Age and female are independently associated with PVD occurrence.

Eyelid tumours and pseudotumours in Hong Kong: a ten-year experience.

OBJECTIVE: To describe the clinicopathological characteristics of patients with eyelid tumours in Hong Kong. DESIGN: Retrospective case series. SETTING: A tertiary eye centre in Hong Kong. PATIENTS: A computerised retrieval system was used to identify all patients who underwent eyelid mass excisions with histological reports, encountered in the period 2000 to 2009, in a tertiary eye centre. The demographics (age, gender), clinical features (laterality, tumour topography), and the pathological diagnosis of each patient were documented. Descriptive statistical tabulation and analyses were performed on the data. RESULTS: In all, 198 patients were identified; all were Chinese. Their mean age was 54 years for benign lesions and 68 years for malignant ones. Women were more commonly affected. Benign tumourous lesions occurred more commonly on the upper (n=91; 54%) than lower eyelid (n=79; 47%), whereas malignant lesions more often affected the lower (n=17, 61%) than upper (n=11, 39%) eyelid. The distribution of left and right eye involvement was similar (103 vs 101, respectively). In six patients, there were bilateral benign lesion. Regarding benign masses, 45 (27%) were intradermal neavi, 38 (22%) were squamous papillomas, 25 (15%) were seborrhoeic keratosis lesions, 14 (8%) were epidermoid cysts, and 7 (4%) were compound naevi. Regarding malignant eyelid tumours, the most common was basal cell carcinomas (n=12, 43%), 5 (18%) were squamous cell carcinomas, 3 (11%) were actinic keratosis lesions, and 2 (7%) each were sebaceous gland carcinomas and melanomas. CONCLUSION: Benign lesions constituted the majority of these eyelid tumours. Among the malignant lesions, basal cell carcinoma was the commonest type, with lower lid involvement in majority. Sebaceous gland carcinoma is not rare, which is in contrast to Caucasian populations. The relative frequencies of the most common malignant tumours in Hong Kong differed substantially from those reported in other Asian studies.

Clinical characteristics of intermediate uveitis in Chinese patients.

PURPOSE: To describe the clinical characteristics of Chinese patients with intermediate uveitis (IU). METHODS: Retrospective review of patients with IU with at least 6 months follow-up. RESULTS: Seventy patients were identified and the mean follow-up was 59.7 months. The mean age at presentation was 33.1 years. Fifteen (21.4%) patients had disease onset before the age of 18 years; 91.4% of IU cases were considered idiopathic after investigations. At the last follow-up, 85 (74.6%) eyes retained vision of at least 20/40. Poor visual outcome was significantly associated with poor presenting visual acuity (p = .002), presence of epiretinal membrane or atrophic macular changes (p = .003), persistent cystoid macular edema (p = .015), and increased disease duration (odds ratio = 1.015 per month, p = .002). Pediatric patients were more likely to have bilateral (p = .003) and chronic disease (p < .001). CONCLUSIONS: IU in Chinese patients was mainly idiopathic, with good visual outcomes in most patients after appropriate treatment.

Lifestyle modification, nutritional and vitamins supplements for age-related macular degeneration.

PURPOSE: To provide a systematic review of the published studies pertaining to the lifestyle modification, dietary, nutritional and vitamins supplements for preventing occurrence or halting deterioration of age-related macular degeneration (AMD). METHODS: The literature searches from 1990 to December 2010 with following keywords, 'age related macular degeneration', 'nutrition', 'antioxidant', 'diet' and 'vitamins supplements' using search engines Pubmed, Google Scholar, Medline and the Cochrane Library. Meta-analyses, population-based cohort studies and case-controlled trials were reviewed, whereas small cases series, case reports, commentaries, abstracts in proceedings or personal observations were excluded. RESULTS: Smoking and obesity are identified risk factors for AMD. High dietary intakes of omega-3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalence and incidence in AMD. Vitamin B and extracts from wolfberry, Gingko biloba and berry anthocyanins were also subjects of intense research interests, but there has been no concluding scientific evidence yet. The Age-Related Eye Disease study (AREDS) is the only large-scale randomized controlled clinical trial to show beneficial effect of AREDS formulation of vitamins C, E, beta-carotene and zinc with copper in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye. CONCLUSION: Quit smoking is an important advice to patients to prevent or slow the progress of AMD. There is no recommendation for routine nutritional or vitamins supplementation for primary prevention. However, patients with documented intermediate risk of AMD or advanced AMD in one eye are recommended to take AREDS-type vitamin supplements.

Associations of the C2-CFB-RDBP-SKIV2L locus with age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To investigate the associations of the C2-CFB-RDBP-SKIV2L region with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). DESIGN: Cross-sectional, case-control association study. PARTICIPANTS: A Chinese case-control group of 200 neovascular AMD patients, 233 PCV patients, and 275 control subjects. METHODS: An association analysis was performed of the C2-CFB-RDBP-SKIV2L locus with both neovascular AMD and PCV in a Chinese population using 19 haplotype-tagging single nucleotide polymorphisms (SNPs) and 6 previously reported SNPs across the C2-CFB-RDBP-SKIV2L region. All SNPs were genotyped using the TaqMan genotyping technology (TaqMan; Applied Biosystems [ABI], Foster City, CA). MAIN OUTCOME MEASURES: Allele and haplotype frequencies of the SNPs in the C2-CFB-RDBP-SKIV2L region. RESULTS: The SKIV2L SNPs rs429608 and rs453821 were significantly associated with neovascular AMD (P = 7.39 × 10(-5); odds ratio [OR], 0.22; 95% confidence interval [CI], 0.10-0.50; and P = 0.001; OR, 0.38; 95% CI, 0.21-0.70, respectively), whereas borderline associations were detected for C2 rs547154 (P = 0.002) and RDBP rs760070 (P = 0.003). Conditional haplotype analysis revealed that SKIV2L rs429608 could account fully for the global haplotype association identified in this region. The association of SKIV2L rs429608 with neovascular AMD remained significant after adjusting for CFH rs800292 and HTRA1 rs11200638. No individual SNP or haplotype was associated significantly with PCV. CONCLUSIONS: In this concurrent investigation of the associations of the entire C2-CFB-RDBP-SKIV2L region with neovascular AMD and PCV, the results suggested that SKIV2L is a likely causal gene for neovascular AMD, conferring a significant protective effect independent of CFH and HTRA1. These data do not support a significant role of this region in PCV, suggesting different molecular mechanisms between neovascular AMD and PCV.

Association of genetic variants on 8p21 and 4q12 with age-related macular degeneration in Asian populations.

PURPOSE: To evaluate the association of genetic variants at chromosomes 8p21 and 4q12 with the risk of developing AMD and its two main subtypes, choroidal neovascular membrane (CNV) and polypoidal choroidal vasculopathy (PCV), in Asian populations. METHODS: The study population comprised 2360 patients with neovascular AMD (1013 typical AMD-CNV and 1282 PCV), and 3598 controls from four independent cohorts, two of Japanese (n = 4859) and two of Chinese (n = 1099) ethnicity. We performed a meta-analysis in case-control studies of two reported single nucleotide polymorphisms (SNPs) (rs13278062 at TNFRSF10A-LOC389641 on 8p21 and rs1713985 at REST-C4orf14-POLR2B-IGFBP7 on 4q12) by using logistic regression analysis adjusted for age and sex. Subgroup analysis by CNV and PCV subtypes were performed to evaluate the significance of these two variants. RESULTS: The reported association between rs13278062 at 8p21 and neovascular AMD was replicated in this population (P = 1.12 × 10(-4), odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.70-0.89). However, there was no association of rs1713985 at 4q12 with neovascular AMD, or its two subtypes, typical AMD-CNV and PCV (all P > 0.05). The study sample size had a statistical power of greater than 99% to detect an association of a risk allele with AMD with an OR of 1.30, as reported in the original study of rs1713985 and AMD. CONCLUSIONS: The present results did not replicate the reported association between rs1713985 at 4q12 and neovascular AMD. However, we confirmed the association between rs13278062 at 8p21 and neovascular AMD in Asian populations.

Differentiation of exudative age-related macular degeneration and polypoidal choroidal vasculopathy in the ARMS2/HTRA1 locus.

PURPOSE: differentiate the associations of exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) with the ARMS2/HTRA1 locus. METHODS: The entire ARMS2 sequence was sequenced and HTRA1 rs11200638 genotyped in 568 unrelated Chinese individuals: 156 exudative AMD patients, 164 PCV patients, and 248 controls. A meta-analysis was performed to examine the effects of rs10490924 and rs11200638 at the ARMS2/HTRA1 locus in PCV. RESULTS: In total, 31 polymorphisms in ARMS2 were identified. Significant associations with both exudative AMD and PCV were observed in 11 of them and HTRA1 rs11200638, with different genotypic distributions between exudative AMD and PCV (P < 0.001). After adjusting for rs11200638, ARMS2 rs10490924 remained significantly associated with exudative AMD (P = 0.011), but not with PCV (P = 0.077). Meta-analysis showed consistent allelic associations of rs10490924 and rs11200638 with PCV in different study populations. CONCLUSIONS: There is a strong and consistent association of the ARMS2/HTRA1 locus with both exudative AMD and PCV, suggesting the two disorders share, at least partially, similar molecular mechanisms. Different effect sizes indicate the existence of additional genetic and environmental factors affecting them to different extents.

Combined high-dose sub-tenon triamcinolone, intravitreal bevacizumab, and laser photocoagulation for refractory diabetic macular edema: a pilot study.

PURPOSE: To study the efficacy and safety of triple therapy (sub-Tenon triamcinolone [∼70 mg], intravitreal bevacizumab [1.25 mg], and focal/grid laser) for refractory diabetic macular edema. METHOD: Twenty-nine eyes of 29 patients who received triple therapy were monitored for central foveal thickness, best-corrected visual acuity (BCVA), and side effects over a 1-year period. Their results were compared with a focal/grid laser historical control group of 18 eyes (18 patients). RESULTS: In the triple therapy group, mean central foveal thickness significantly reduced from baseline value of 441 µm to 298 µm at Month 12 (P < 0.001), but there was no significant change of BCVA. In the control group, there were no sustained significant changes of central foveal thickness or BCVA. A subgroup analysis of 7 eyes in the triple therapy group with baseline BCVA of ≤20/100 showed significant BCVA improvements from 4 weeks to 9 months. The maximum improvement was achieved at 6 months, when the mean BCVA improved by 9.5 Early Treatment Diabetic Retinopathy Study letters from baseline. Intraocular pressure rise (31.0%), partial ptosis (17.2%), and significant cataractogenesis (8.7%) were encountered in the triple therapy group but not in the control group. CONCLUSION: Sustained reduction of central foveal thickness was achieved with triple therapy over the 1-year study period. Significant visual improvement was seen only in patients with worse baseline BCVA, but not in the triple therapy group as a whole. Significant side effects of intraocular pressure rise, ptosis, and cataractogenesis were encountered in the triple therapy group.

Effectiveness of diode laser trans-scleral cyclophotocoagulation in patients following silicone oil-induced ocular hypertension in Chinese eyes.

We evaluated the effectiveness of diode laser trans-scleral cyclophotocoagulation (TSCPC) on intraocular pressure (IOP) in nine patients having raised IOP following use of silicone oil (SO) for retinal detachment (RD) surgery in a retrospective observational case series. Diode laser TSCPC was applied at a power setting of 1.75 to 2.5 watts, for two sec with a maximum of 30 applications. The patients were followed up for 40 to 312 weeks. The mean pre-laser IOP was 32.06 mm Hg (SD 7.32). The mean post-laser IOP at one month, three months and six months was 17.89 mm Hg (SD 8.23), 21.89 mm Hg (SD 8.16) and 21.67 mm Hg (SD 7.55) respectively. The final IOP (at the last follow-up) was 19.56 mm Hg (SD 7.85) (P=0.021). Seven of them had undergone SO removal. In our observation, effectiveness of TSCPC in long-term control of SO-induced ocular hypertension was limited as compared to short-term control of IOP.

Photodynamic therapy with or without intravitreal triamcinolone acetonide for symptomatic polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the outcome of verteporfin photodynamic therapy (PDT) with or without intravitreal triamcinolone acetonide (IVTA) for the treatment of symptomatic polypoidal choroidal vasculopathy (PCV). METHODS: Retrospective analysis of PCV patients who underwent PDT with or without IVTA with follow-up of 2 or more years. Changes in best-corrected visual acuity (BCVA), proportion of eyes with moderate visual loss (3 or more lines), and complications were compared between patients with or without IVTA. RESULTS: Twenty-seven eyes of 27 patients were analyzed, with 12 eyes treated by PDT monotherapy and 15 eyes treated by combined PDT with IVTA. The baseline characteristics of both groups were similar. At 1 year, the mean logMAR BCVA for the PDT monotherapy group improved from 0.74 to 0.58 (P = 0.011), whereas the combined PDT and IVTA group improved from 0.84 to 0.74 (P = 0.17). At 2 years, the mean logMAR BCVA for the monotherapy and combined treatment groups were 0.62 and 0.84, respectively, and the changes compared with baseline were not statistically significant. No significant difference was found in the mean logMAR BCVA, the mean line of visual changes, and the mean number of PDT treatments between the 2 groups at 1 and 2 years. One (8.3%) and 4 (26.7%) eyes in the monotherapy and the combined groups lost 3 or more lines at 2 years, respectively. Patients who had combined PDT with IVTA were more likely to develop cataract requiring surgery and ocular hypertension (P = 0.043 and 0.046, respectively). CONCLUSIONS: PDT reduced the risks of visual loss in patients with symptomatic PCV in the short term but the effect might not be sustained after 1 year. The adjunctive use of IVTA during PDT did not appear to result in additional benefit for treating PCV.

Visual outcomes and growth factor changes of two dosages of intravitreal bevacizumab for neovascular age-related macular degeneration: a randomized, controlled trial.

PURPOSE: To evaluate the visual and growth factor changes of two different intravitreal bevacizumab dosages for neovascular age-related macular degeneration. METHODS: Fifty eyes of 50 patients with neovascular age-related macular degeneration were randomized to receive 3 monthly intravitreal injections of 1.25 mg (24 eyes) or 2.5 mg (26 eyes) bevacizumab. Patients were observed for 6 months, and the logarithm of minimal angle of resolution best-corrected visual acuity, central foveal thickness, aqueous vascular endothelial growth factor, and pigment epithelial derived factor levels were assessed. RESULTS: Both groups had significant central foveal thickness reductions at 6 months (P < 0.001). Six (23.1%) eyes in the 2.5-mg group lost 3 or more lines compared with none in the 1.25-mg group (P = 0.023). No significant difference in logarithm of minimal angle of resolution best-corrected visual acuity, central foveal thickness, or growth factors levels was found between the two groups at all visits. Eyes with persistent angiographic leakage at 3 months had significantly higher baseline aqueous vascular endothelial growth factor levels compared with eyes without leakage (P = 0.013). Logistic regression analysis showed that high baseline aqueous vascular endothelial growth factor level was the only significant factor associated with persistent leakage at 3 months (P = 0.040). CONCLUSION: Three monthly intravitreal 1.25-mg bevacizumab injections seemed to result in better visual outcome than 2.5 mg bevacizumab. Baseline aqueous vascular endothelial growth factor level might have a role in predicting angiographic response after bevacizumab injections.

Factors associated with variability in response of diabetic macular oedema after intravitreal triamcinolone.

PURPOSE: To identify factors associated with variability in anatomical and functional response of diabetic macular oedema (DMO) after 4 mg of intravitreal triamcinolone acetonide (ivTA), and for recurrence of macular oedema. DESIGN: Pooled analysis of individual data from two randomized controlled trials. METHODS: This was a multicentre study involving 107 eyes with DMO administered 4 mg ivTA. Predictive factors for response to treatment were evaluated with linear regression analysis. Factors associated with time to recurrence of oedema were studied with Cox proportional hazards modelling. Main outcome measures were maximum improvement in optical coherence tomography (OCT)-measured central foveal thickness (CFT) and best-corrected visual acuity (BCVA), final CFT and BCVA at 12 months and time to oedema recurrence. RESULTS: Greater reduction of retinal thickening occurred in eyes with worse baseline thickening (P < 0.001). There was also greater improvement of visual acuity in eyes with poorer preoperative BCVA levels (P < 0.001). Age, duration of oedema and previous macular laser treatment had no significant effect on maximal BCVA or CFT improvement. Eyes given 4 mg triamcinolone alone were more likely to develop recurrence of oedema at 12 months than those given a combination of 4 mg triamcinolone plus sequential laser (hazard ratio 2.60 [95% confidence interval: 1.45-4.67]). CONCLUSION: Baseline OCT-measured retinal thickening and BCVA are important predictors of maximal anatomical and functional response of DMO to ivTA, respectively. Combination treatment strategy using sequential laser therapy may have a role in delaying recurrence of oedema after triamcinolone.

Intravitreal ranibizumab for the primary treatment of choroidal neovascularization secondary to pathologic myopia.

PURPOSE: To evaluate the efficacy of intravitreal ranibizumab for the primary treatment of myopic choroidal neovascularization (CNV). METHODS: Sixteen eyes of 16 consecutive patients who received 3 monthly injections of intravitreal ranibizumab for primary treatment of myopic CNV were reviewed. Additional ranibizumab injections were performed in eyes with persistent or recurrent CNV after 3 months. RESULTS: The mean age of the patients was 60.8 years, and the spherical equivalent refractive error was -10.9 D. The mean logMAR best-corrected visual acuity at baseline was 0.58 (20/76). At 1 month and 12 months, the mean logMAR best-corrected visual acuity improved significantly to 0.39 (20/49) and 0.28 (20/37), respectively (P = 0.001 and P < 0.001, respectively). The mean improvement at 12 months was 3.0 lines, and 12 (75.0%) eyes had improvement of 2 or more lines. Fifteen (93.8%) eyes had angiographic closure at 3 months and 1 (6.2%) required further treatment because of persistent leakage at 3 months. Two (12.5%) patients had recurrence of CNV and required retreatment between 3 months and 9 months. Optical coherence tomography showed significant reduction in the mean central foveal thickness after treatment (P < 0.001). None of the patients developed any ocular or systemic side effects associated with intravitreal ranibizumab. CONCLUSION: Intravitreal ranibizumab appeared to be effective for the primary treatment of myopic CNV, with a high proportion of patients sustaining visual gain after treatment.

Central serous chorioretinopathy after sequential argon-neodymium: YAG laser iridotomies.

Laser peripheral iridotomy is the standard treatment for acute angle-closure glaucoma. A patient with acute angle-closure glaucoma who developed central serous chorioretinopathy after uneventful laser iridotomies is described. Central serous chorioretinopathy occurring after sequential argon-neodymium:YAG laser peripheral iridotomy is a novel complication in the English literature and is related to the stress induced by both the initial disease and the subsequent procedure, particularly in psychologically susceptible individuals.