Shabeeba R Hannan

An analysis of the CFH Y402H genotype in AMD patients and controls from the UK, and response to PDT treatment

AimMutation in the complement factor H (CFH) gene is an important risk factor for age-related macular degeneration (AMD). In this study, we identified the strength of the CFH Y402H gene variant association in a UK AMD cohort and tested the hypothesis that this variant may influence the biological response of choroidal neovascularisation (CNV) following photodynamic therapy (PDT) for CNV.MethodsA total of 557 cases with AMD and 551 normal controls were genotyped for the CFH Y402H (1277 C/T) variant using the 5′ nuclease TaqMan assay for allelic discrimination. The CFH gene association for AMD, for the different CNV subtypes and for patients needing PDT was estimated. Twenty-seven PDT-treated patients were followed up for 15 months with ETDRS-derived vision, clinical examination, and fundus angiography. Individuals with different CFH genotypes were then analysed for any association with visual change following PDT.ResultsThe risk association for AMD with the CFH CC genotype (odd ratio (OR)=3.62, Pc<0.0001) was similar to that reported in other Caucasian cohorts. The magnitude and strength of this association was stronger in AREDS stages 2–4 (ORs=4.48, 2.69, and 5.17). ORs for the risk of predominantly classic CNV were significantly raised for both the CC (OR=17.87, P<0.0001) and CT (OR=9.06, P=0.0002) genotypes. The number of patients carrying the high-risk C allele was 70.4% in those requiring PDT as compared to 52.3% in the non-PDT group (OR=2.16, P=0.011), and presence of the CC genotype significantly increased the risk of PDT (OR=5.48, P=0.015). The degree of visual loss following PDT was significantly higher in the CFH CC genotype group (P=0.038); 50% of CC cases (n=13) and 45% of the CT cases (n=12) lost 15 or more ETDRS letters at final follow-up.ConclusionIn this UK cohort of AMD patients, the CFH Y402H variant was significantly enriched in patients with predominantly classic CNV. Patients homozygous for the CFH Y402H genotype seem to have worse visual acuity after PDT.

Interleukin 8 promoter polymorphism -251A/T is a risk factor for age related macular degeneration.

Background/aims: To determine whether four expression-related cytokine polymorphisms are associated with age-related macular degeneration (AMD). Methods: DNA from 478 cases with AMD and 555 normal controls was genotyped for the pro-inflammatory IL1β −511C/T, IL6 −174C/G, IL8 −251A/T and anti-inflammatory IL10 −1082G/A cytokine polymorphisms using the 5′ nuclease TaqMan® assay for allelic discrimination. Associations with AMD were analysed using allelic frequencies. Results: The −251A allele of the IL8 promoter gene polymorphism was more prevalent in AMD patients than controls (p = 0.037, OR = 1.21, 95% CI = 1.01 to 1.44). Adjusting for age, sex, body mass index (BMI), current smoking and past smoking status did not alter the AMD association significantly (corrected p value = 0.043, OR = 1.23, 95% CI = 1.0 to 1.50). Conclusion: The pro-inflammatory homozygous IL8 –251AA genotype is an important risk factor for AMD. This may have implications for future therapy with biological agents that could target this cytokine.

Intravitreal bevacizumab (Avastin) for the treatment of choroidal neovascularization in age-related macular degeneration: results from 118 cases

Several vascular endothelial growth factor inhibitors have recently been studied as treatments for neovascular AMD.1 2 Pegaptanib sodium improved visual acuity in 6% of patients at one year;1 Ranibizumab 0.5 mg improved vision by three lines in 33% of patients at one year.2 Michels et al. 3 initially reported the use of intravenous bevacizumab for the treatment of choroidal neovascularization (CNV), and others have found visual improvement and reduction in macular thickness with intravitreal bevacizumab.4–8 We present the results from 118 cases treated with intravitreal bevacizumab based at a single centre. A retrospective review of 115 consecutive patients (118 eyes) based at Southampton Eye Unit, treated with intravitreal bevacizumab for CNV was performed. Lesions of all types irrespective of size or location that were either ineligible for photodynamic therapy (PDT) under the National Health Service (including minimally classic and occult CNV) or those not responding to PDT (classic or predominantly classic CNV with recurrent or persistent CNV activity) were included in the study (table 1). All patients underwent visual acuity testing (best corrected Snellen), slitlamp examination and fundus fluorescein angiography. Central macular thickness (CMT) was assessed using Stratus optical coherence tomography (Carl Zeiss Meditec, USA). View this table: Table 1 Baseline characteristics After discussion about the off-label nature of treatment and the potential risks, informed …

Idiopathic juxtafoveolar retinal telangiectasis in monozygotic twins

Monozygotic twins (aged 63 years old), with group-2A idiopathic juxtafoveolar retinal telangiectasia (JXT), underwent clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). Twin 1 : Right fundus showed right-angled venules temporal to the fovea; FA demonstrated retino-retinal anastomosis and intraretinal leakage. Twin 2 : Fundoscopy revealed right-angled venules in both eyes. OCT demonstrated foveal cysts in all eyes. This is the third set of monozygotic twins with group-2A JXT that has been reported in the literature, further supporting a genetic predisposition for JXT. The twin who smoked had more severe disease, suggesting that smoking is a risk factor for progression. OCT is useful in the detection and monitoring of these patients. Group-2A JXT is characterised by bilateral regions of retinal thickening …

Common spectral domain OCT and electrophysiological findings in different pattern dystrophies

Objectives (1) To investigate and integrate the tomographic, angiographic and electrodiagnostic findings in pattern dystrophy. (2) To correlate visual acuity (VA) with central macular thickness (CMT), the electrooculogram (EOG) and pattern electroretinogram (PERG). Design A retrospective study of patients with pattern dystrophy. 52 eyes of 26 patients were examined. Results Thirty-three eyes had adult-onset foveomacular vitelliform dystrophy, 8 had multifocal pattern dystrophy, 6 had butterfly pattern dystrophy and 2 had reticular pattern dystrophy. SD-OCT demonstrated hyperreflectivity between the retinal pigment epithelium (RPE)/ Bruchs complex, and the junction of the inner and outer segments (IS/OS) of the photoreceptors. Disruption of the IS/OS was observed in 20, and disruption of the end tips of photoreceptors was clearly visible in eight eyes. 11 eyes showed abnormal focal hyper-reflectivity originating from the RPE towards the outer nuclear layer (ONL), and in two eyes this appeared to originate from the junction of the IS/OS towards the ONL. EDTs revealed borderline or a reduced EOG in 25 (51%) and a degraded PERG in 41eyes (83.6%) with the P50 component reduced in 23 and N95 in 18. CMT and Arden ratio did not show any significant correlation with VA. Conclusions We observed relatively consistent features between different types of pattern dystrophies. In addition we observed novel findings on 3D-OCT. We also report 3D-OCT features of reticular, multifocal and butterfly pattern dystrophies. The degraded PERG results observed in our study indicate that the disease process in this condition is not limited to the RPE.

Can optical coherence tomography predict the outcome of laser photocoagulation for diabetic macular edema

BACKGROUND AND OBJECTIVE To compare the effectiveness of augmented superior oblique Z-tenotomy (SOZT) with fixed standard SOZT in canceling preoperative superior oblique overaction associated with A pattern anisotropia or V pattern in Browns syndrome. PATIENTS AND METHODS Sixteen consecutive patients with superior oblique overaction or Browns syndrome were treated by removal of a triangular piece of the superior oblique tendon near its insertion (augmented SOZT). Outcome was compared with 20 consecutive historical controls after standard SOZT. RESULTS The decrease in superior oblique overaction in the right and left eyes and fundus intorsion and the collapse of A pattern anisotropia were more significant for patients with superior oblique overaction (P = .003, P = .007, P = .05, P = .0015, respectively) and patients with Browns syndrome (P = .025, P = .03, and P = .05, respectively). No study patient with superior oblique overaction and A pattern anisotropia required reoperation compared with 5 of 14 controls (37.5%); rates for patients with Browns syndrome were 0 for the study group and 3 of 6 (50%) for the control group. CONCLUSIONS Augmented SOZT is superior to standard SOZT for correcting superior oblique overaction, intorsion, A or V pattern, and stereopsis. It is not associated with complications or reoperation. The size of the Z-tenotomy can be modified according to the intraoperative assessment to achieve symmetric results.

Retinal pigment epithelial tear following intravitreal bevacizumab for choroidal neovascular membrane due to age-related macular degeneration

Retinal pigment epithelium (RPE) tears are an uncommon but visually damaging complication of pigment epithelial detachment (PED), caused by weak atrophic margins of chronic PED and contraction of sub-RPE fibrovascular scar tissue. RPE tears can occur spontaneously or following treatment of the choroidal neovascular (CNV) membrane. There have been reports of RPE tears following laser photocoagulation,1 transpupillary thermotherapy,2 photodynamic therapy with or without combined intravitreal triamcinolone3,4 and intravitreal Macugen.5 We report a case of a patient with PED with submacular haemorrhage and occult CNV who developed an RPE tear following intravitreal bevacizumab (Avastin). A 74-year-old man presented with a 10-day history of diminished right visual acuity. The corrected visual …

Retinal angiomatous proliferation occurring after radiotherapy.

PurposeTo describe two cases of retinal angiomatous proliferation (RAP)-like lesion following radiation therapy for primary tumor.Patients and methodsRetrospective evaluation of two patients with previous irradiation treatment for a pleomorphic adenoma of the lacrimal gland and a vocal cord carcinoma, respectively. Visual acuity (VA), fluorescein angiography and optical coherence tomography were performed and demonstrated a RAP-like lesion in both cases. Treatment with intravitreal injections of Ranibizumab was performed with a follow-up of 19 and 10 months, respectively.ResultsBoth the patients had a positive response to the treatment with improvement in VA and reduction of intraretinal fluid.ConclusionRAP-like lesions can develop following radiation treatment for a primary tumor. In patients presenting with idiopathic RAP, a history of prior radiotherapy should be considered.