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.

Choroidal thickness measurement in myopic eyes by enhanced depth optical coherence tomography.

PURPOSE: To measure choroidal thickness (CT) in myopic eyes using enhanced depth imaging (EDI). DESIGN: A cross-sectional study. PARTICIPANTS: Fifty-six consecutive patients with spherical equivalent refractive error of at least 6 diopters (D) were evaluated. METHODS: Enhanced depth imaging optical coherence tomography (OCT) images were obtained by positioning the spectral-domain OCT device close enough to the eye to acquire an enhanced signal of the choroidal layer. Choroidal depth was measured as the distance between the outer reflective retinal pigment epithelium (RPE) layer and the inner sclera border. Measurements were made in a horizontal fashion across the fovea at 500-µm intervals of the sections. The CT was measured at the subfoveal region in a horizontal fashion, 3 mm temporal to fovea and 3 mm nasal to fovea. MAIN OUTCOME MEASURES: Correlations among CT with age, refractive error in diopters, and visual acuity in logarithm of the minimum angle of resolution (logMAR) were analyzed with linear mixed models. RESULTS: The mean age of the 56 patients was 50.4 years (± 2.03 years standard deviation; interquartile range [IQR], 42-62 years), and the mean refractive error was -8.7 D (IQR, -6.1 to -11 D). The mean subfoveal CT was 118 µm (± 68 µm) and correlated negatively with age (P = 0.032) and refractive error (P = 0.011). Regression analysis suggested that subfoveal CT decreased by 11.9 µm for each decade of life and by 6.205 µm for each diopter of myopia. The subfoveal CT was inversely correlated with the logMAR visual acuity (P = 0.008), and visual acuity improved by 0.02 (logMAR) in a 10-µm increase in CT. CONCLUSIONS: Choroidal thickness decreases with age and severity of myopia. Visual acuity decreases in line with decreasing subfoveal CT. A reduction in CT is related to aging and the severity of myopia, whereas visual acuity depends on subfoveal CT. Our study supports the theory that choroidal abnormality may play a key role in the pathogenesis of myopic degeneration. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

Review of Intermediate Uveitis.

The purpose of this article is to highlight evidence about the medical and surgical management of intermediate uveitis (IU). Updated understandings of the immunopathology of IU were reviewed in this retrospective literature review. Literature selection for this review was based on the PubMed database (National Library of Medicine) and OVID database (Wolters Kluwer). Articles deemed relevant were selected and highlighted. Intermediate uveitis is most often a benign form of uveitis. Since intermediate uveitis has been described in association with different systemic disorders, the initial diagnostic evaluation should serve to exclude masquerade syndromes and infectious diseases in which immunosuppression may be ineffective or contraindicated. Although the pathogenesis of intermediate uveitis is not fully understood, identification of proinflammatory molecules involved in the IU has contributed to the development and implementation of new therapies. Studies about the use of various immunosuppressants, biological agents and surgical treatment on IU have provided more evidence for managing IU. Nevertheless, corticosteroids remain the mainstay of treatment. The treatment options of intermediate uveitis are evolving, with the development of various immunosuppressants and biological agents. The management of intermediate uveitis should be tailored individually, based on specific causes of the disease and associated complications.

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.

Prospective Randomized Comparative Study of the Effect of Pupil Dilation or Miosis in Intraocular Lens Pupillary Capture After Combined Phacoemulsification and Vitrectomy With Intraocular Tamponade.

PURPOSE: The objective of the study was to compare the safety and efficacy of postoperative pharmacological pupil dilation, miosis, and alternate-day pupil dilation and miosis after combined phacoemulsification (phaco), intraocular lens (IOL) implantation, and pars plana vitrectomy (PPV) with intraocular tamponade. DESIGN: This was a prospective, randomized controlled clinical trial. METHODS: Patients who were indicated for phaco with IOL implantation, PPV, and intraocular tamponade were randomly assigned into 3 different groups: (1) pupil dilation using 4% homatropine (dilation group), (2) pupil miosis using 1% pilocarpine (miosis group), and (3) alternate-day pupil miosis and dilation starting with 1% pilocarpine on the first day postoperatively and switched to 4% homatropine thereafter on alternate days (alternate-day group). The main outcome measured was the rate of IOL capture postoperatively. The secondary measurable outcomes were the complication rates, visual acuity, and ease of fundal examination with binocular indirect ophthalmoscopy. RESULTS: Twenty-two, 21, and 20 eyes were allocated to the dilation, miosis, and alternate-day groups, respectively. Intraocular lens capture was found in 7 (11.1%) of 63 eyes. Intraocular lens was captured in 6 (27.3%) of 22 eyes in the dilation, 1 (4.5%) of 21 eyes in the miosis, and none in the alternate-day groups (P = 0.0133). The difference of the visual acuity among the 3 groups was not statistically significant (P = 0.650). Anterior chamber reaction of more than +1 cell in the first week was found in 6 (27.3%) of 22, 13 (61.9%) of 21, and 10 (50%) of 20 eyes in the dilation, miosis, and alternate-day groups, respectively (P = 0.074). Although more eyes were found with posterior synechia in the miosis group, the difference was not statistically significant (P = 0.478). The number of eyes that had suboptimal binocular indirect ophthalmoscopy view was 3 (13.6%) of 22, 12 (57.1%) of 21, and 6 (30%) of 20 in the dilation, miosis, and alternate-day groups, respectively (P = 0.01). CONCLUSIONS: Pupil dilation after combined phaco with IOL implantation, PPV, and intraocular tamponade could lead to a higher chance of IOL capture. Pupil miosis may lead to more anterior chamber inflammation. The regimen of alternate pupil dilation and miosis may cause less chance of IOL capture.

Review of Clinical Features, Microbiological Spectrum, and Treatment Outcomes of Endogenous Endophthalmitis over an 8-Year Period.

Purpose. To evaluate the clinical features, microbiological spectrum, and treatment outcomes of endogenous endophthalmitis. Methods. Retrospective review of consecutive cases with infective endogenous endophthalmitis presenting from 2000 to 2007. The main outcome measure was the visual outcome at the latest follow-up visit. Other outcome measures included microbiological investigations, anatomical and clinical outcomes. Results. 22 eyes of 21 patients were included, and the mean follow-up duration was 2.7 years. Eyes with fungal endogenous endophthalmitis were more likely to have visual acuity of finger counting or better at presentation compared with those with bacterial endogenous endophthalmitis (odds ratio = 15.0, P = 0.013). Gram-negative microorganisms accounted for 50% of infections, while fungal and gram-positive organisms accounted for 27.3% and 22.7%, respectively. Despite treatment, the visual outcome was poor in general as 10 (45.5%) eyes had no light perception at the latest follow-up visit and 6 (27.3%) eyes required enucleation or evisceration. Contrary to previous studies, fungal endogenous endophthalmitis did not appear to have better visual outcome compared with bacterial endogenous endophthalmitis. Conclusion. Gram-negative microorganisms were the main causative pathogens of endogenous endophthalmitis in Hong Kong. The visual prognosis of endogenous endophthalmitis is generally poor as almost 50% of eyes were blind despite treatment.