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.

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.

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.

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.

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.

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.

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.

Efficacy of 1.25 MG versus 2.5 MG intravitreal bevacizumab for diabetic macular edema: six-month results of a randomized controlled trial.

PURPOSE: To evaluate the efficacy of intravitreal injections of two different dosages of bevacizumab (Avastin) for treating diffuse diabetic macular edema. METHODS: Fifty-two eyes of 52 patients with diabetic macular edema were randomized to receive three monthly intravitreal injections of 1.25 mg or 2.5 mg bevacizumab. Patients were observed for 6 months and optical coherence tomography central foveal thickness, logMAR best-corrected visual acuity (BCVA), and adverse events were assessed. RESULTS: Forty-eight eyes of 48 patients completed the 6-month follow-up and were analyzed. Significant mean central foveal thickness reductions were observed in both groups at all follow-up visits (P < 0.013). Significant improvements between baseline and 6-month mean logMAR BCVAs were seen, with the mean logMAR BCVA improved from 0.63 to 0.52 in the 1.25 mg group and 0.60 to 0.47 in the 2.5 mg group. No significant difference in BCVA was observed between the two groups at any time point (P > 0.56). Subgroup analysis showed that intravitreal bevacizumab seemed to be more effective in eyes without any previous diabetic macular edema treatment. CONCLUSIONS: Three monthly intravitreal bevacizumab injections resulted in significant reduction in central foveal thickness and improvements in BCVA in diabetic macular edema patients. Both 1.25 mg and 2.5 mg seemed to have similar treatment efficacy.

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.

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.

HTRA1 variants in exudative age-related macular degeneration and interactions with smoking and CFH.

PURPOSE: Mapping the genes for age-related macular degeneration (AMD) had not been successful until recent genome-wide association studies revealed Tyr402His in CFH and rs11200638 in HTRA1 as AMD-related genetic variants. This study was conducted to identify other critical factors in HTRA1 that are associated with exudative AMD. METHODS: The promoter, splice regions, and coding exons of HTRA1 were sequenced in 163 patients with exudative AMD and 183 sex- and age-matched control subjects. Also documented were the CFH genotype and smoking status. RESULTS: Four significant SNPs were found in the promoter and the first exon of HTRA1: rs11200638 (-625G>A), rs2672598 (-487T>C), rs1049331 (102C>T, Ala34Ala), and rs2293870 (108G>T, Gly36Gly) with respective P = 1.7 x 10(-14), 3.0 x 10(-10), 3.7 x 10(-12), and 3.7 x 10(-12). Among them, rs11200638 is the most significant associated SNP with a high odds ratio (OR) of 7.6 (95% CI: 3.94-14.51). One risk haplotype block across the promoter and exon 1, ACCTT, significantly predisposes to AMD (P = 6.68 x 10(-14)). In both models, significant independent additive effects were identified with smoking and rs800292 (184G>A, Val62Ile) of CFH. Smoking and rs11200638 (HTRA1) combined caused a 15.7-fold increased risk, whereas combined rs800292 and rs11200638 caused a 23.3-fold increased risk. An extremely high population attributable risk (PAR) of 78% was also found. CONCLUSIONS: A high impact of the additive effect of CFH and HTRA1 in the development of exudative AMD was shown. The HTRA1-smoking additive effect found in this study further suggests the importance of this environmental risk factor in AMD.

EDN1 Lys198Asn is associated with diabetic retinopathy in type 2 diabetes.

PURPOSE: We tested the hypothesis that genetic variants in vasoactive and angiogenic factors regulating the retina vasculature contribute to the development of diabetic retinopathy (DR). METHODS: A case-control study was performed to study the genetic association between DR and polymorphic variants of EDN1 (Lys198Asn), LTA (IVS1-80C>A, IVS1-206G>C, IVS1-252A>G), eNOS (Glu298Asp), and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well defined population with type 2 diabetes, consisting of 127 controls and 216 DR patients, was recruited. RESULTS: A higher frequency of the Asn/Asn genotype of EDN1 was found in individuals with at least 10 years of diabetes and no retinopathy (controls) compared with DR patients with any duration of diabetes (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic regression analysis showed that the Asn/Asn genotype was the factor most significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07-0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys + Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008). The distributions of Lys198Asn alleles in hypertension did not differ from normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS, or ITGA2 were detected, and there were no detectable gene-gene or gene-environmental interactions among the polymorphisms. CONCLUSIONS: The Asn/Asn genotype of EDN1 was associated with a reduced risk of DR and with delayed onset of type 2 diabetes.

Half-dose verteporfin photodynamic therapy for acute central serous chorioretinopathy: one-year results of a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of photodynamic therapy (PDT) with half-dose verteporfin for treating acute central serous chorioretinopathy (CSC). DESIGN: Prospective, double-masked, placebo-controlled, randomized clinical trial. PARTICIPANTS AND CONTROLS: Sixty-three eyes of 63 patients with acute symptomatic CSC of 3 months' duration or less were recruited. Forty-three eyes were randomized to indocyanine green angiography (ICGA)-guided PDT with half-dose (3 mg/m(2)) verteporfin and 21 eyes were randomized to placebo. INTERVENTION: Patients in the verteporfin group received an infusion of half-dose verteporfin over 8 minutes, followed by ICGA-guided PDT 10 minutes from the start of infusion. Laser was applied for 83 seconds covering the choroidal abnormalities observed in ICGA, with a maximum laser spot size of 4500 mum. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of eyes with absence of subretinal fluid at the macula at 12 months. Secondary outcome measures included changes in mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), subjective symptoms, optical coherence tomography (OCT) results, central foveal thickness (CFT), and angiographic findings during the 12-month study period. RESULTS: Thirty-nine patients in the verteporfin group and 19 patients in the placebo group completed 12 months of follow-up. Thirty-seven (94.9%) eyes in the verteporfin group compared with 11 (57.9%) eyes in the placebo group showed absence of subretinal fluid at the macula at 12 months (P = 0.001). The mean logMAR BCVA at 12 months was significantly better in the verteporfin group compared with the placebo group: -0.05 and 0.05, respectively (P = 0.008). All 39 (100%) verteporfin-treated eyes had stable or improved vision, compared with 15 (78.9%) eyes in the placebo group (P = 0.009). The mean OCT CFT for the verteporfin group also was significantly lower compared with the placebo group at 12 months (P = 0.001). No ocular or systemic adverse event was encountered in the study. CONCLUSIONS: Photodynamic therapy with half-dose verteporfin is effective in treating acute symptomatic CSC, resulting in a higher proportion of patients with absence of exudative macular detachment and better visual acuity compared with placebo.

Changes in aqueous vascular endothelial growth factor and pigment epithelial-derived factor levels following intravitreal bevacizumab injections for choroidal neovascularization secondary to age-related macular degeneration or pathologic myopia.

BACKGROUND: To evaluate the changes in aqueous vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) following intravitreal bevacizumab injections for choroidal neovascularization (CNV) secondary to age-related macular degeneration or pathologic myopia. METHODS: Aqueous samples were obtained at the time of injection from 51 eyes of 51 patients who underwent three monthly intravitreal bevacizumab (Avastin) injections at baseline, 1, and 2 months. Concentrations of VEGF and PEDF in the aqueous were evaluated using enzyme-linked immunosorbent assay and compared. RESULTS: For the 34 eyes with age-related macular degeneration CNV, the mean +/- standard deviation aqueous VEGF level reduced from 102.6 pg/mL +/- 90.6 pg/mL at baseline to 18.3 pg/mL +/- 22.5 pg/mL at 2 months (P < 0.001), whereas the mean PEDF level increased from 11.2 ng/mL +/- 10.4 ng/mL at baseline to 38.7 ng/mL +/- 47.9 ng/mL at 2 months (P = 0.001). For the 17 eyes with myopic CNV, the mean +/- standard deviation aqueous VEGF level reduced from 20.1 pg/mL +/- 28.9 pg/mL at baseline to 3.8 pg/mL +/- 5.3 pg/mL at 2 months (P = 0.016), whereas the mean PEDF level increased from 20.0 ng/mL +/- 16.3 ng/mL at baseline to 126.0 ng/mL +/- 152.0 ng/mL at 2 months (P = 0.016). CONCLUSIONS: Intravitreal bevacizumab injections resulted in reduced aqueous VEGF and increased PEDF levels in patients with CNV secondary to age-related macular degeneration or pathologic myopia. These changes may be favorable for the inhibition of CNV angiogenesis.

Retrocapsular lens matter in uneventful phacoemulsification: does it really exist?

PURPOSE: To have the first cytopathological evaluation of any lens matter fragments within retrocapsular anterior vitreous in those patients undergone uneventful phacoemulsification in Prince of Wales Hospital, Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong. METHODS: Thirty patients with cataracts and various vitreoretinal conditions that required combined surgery were recruited. After the uneventful clear corneal phacoemulsification, three sclerotomies including infusion port were created with cautions against any inadvertent leakage of vitreal content. The anterior vitreous at retrocapsular space was harvested by a special 'round-the-clock' dry vitrectomy into a special specimen reservoir hub and syringe. The aspirate was immediately fixed in 50% ethanol and together with a masked positive control sent for cytocentrifugation processing. The microscope slides of the anterior vitreal content and control were stained with haematoxylin and eosin and papanicolaou. Positive controls were collected from the effluent fluid of the phaco cassettes right after the phacoemulsification. The samples were masked and examined by an experienced pathologist for any cytopathological evidence of lens matter. RESULTS: Out of 30 patients, three suspicious cases of retrocapsular lens fragment were noted by retroillumination on the operating table. However, all the anterior vitreous specimens were negative for lens matter whereas all the controls were positive after cytopathological verification. CONCLUSIONS: This is the first cytopathological study objectively indicating low likelihood of the postulation that retrocapsular lens matter occurred after uneventful phacoemulsification.

Genotype phenotype analysis of Bietti's crystalline dystrophy in patients with CYP4V2 mutations.

PURPOSE: To evaluate the genotypic and phenotypic correlations of Bietti's crystalline dystrophy (BCD) in patients with the CYP4V2 gene by mutation screening and clinical and electrophysiological assessment. METHODS: Eighteen Chinese patients in 13 families with BCD were recruited for full ophthalmic examinations, optical coherence tomography (OCT), and visual electrophysiological tests, including electrooculography (EOG), full-field electroretinography (ERG), and multifocal electroretinography (mfERG). Peripheral venous blood was obtained from all index patients and their family members for genomic DNA extraction and CYP4V2 sequence screening by direct sequencing. RESULTS: All 18 patients with BCD had mutations in the CYP4V2 gene: five were novel (Y219H, W244X, D324V, P396L, and R400C) and four had been reported. A common mutation occurred at the splice site IVS6-8del17bp/insGC of 12 patients, four being homozygous. OCT showed the presence of intraretinal crystals in all patients. Patients with more severe thinning of the retina had worse visual acuity, and there was moderate correlation between the OCT central foveal thickness and visual acuity (Spearman rho = 0.46, P = 0.005). Patients with splice site mutations (i.e., homozygous IVS6-8del17bp/insGC or compound heterozygous IVS6-8del17bp/insGC and IVS8-2A>G) had lower EOG Arden index (P = 0.014) and were more likely to have a nonrecordable scotopic full-field ERG (P = 0.003) and nonrecordable 30-Hz flicker ERG (P = 0.043). CONCLUSIONS: BCD patients with homozygous IVS6-8del17bp/insGC or compound heterozygous IVS6-8del17bp/insGC and IVS8-2A>G mutations appeared to have more severe disease phenotype based on electrophysiological testing. The level of visual loss in BCD is related to the severity of retinal thinning.