A J Luff

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.

Ocular morbidity associated with intravitreal triamcinolone acetonide

AimTo report on the complications associated with the use of intravitreal triamcinolone acetonide (IVTA) in a tertiary referral hospital setting.Materials and methodsA retrospective case series review of all IVTA injections carried out over a period of 30 months.ResultsOne hundred and thirty IVTA injections were performed; nine with limited local follow-up were excluded. Thus, 121 injections (108 patients, 114 eyes) were included in the study. Triamcinolone (4 mg) was used in all cases. Indications were diabetic macular oedema (n=41 eyes), retinal vein occlusions (n=27), postoperative cystoid macular oedema (n=24), exudative age-related macular degeneration (n=16), and others (n=6). No intraoperative complications were recorded. Postoperative intraocular pressure (IOP) readings of 22, 28, 35, and 40 mmHg or higher were recorded in 46.5, 29.8, 12.3, and 7.9% of eyes, respectively. IOP elevation was treated with antiglaucoma medication in all but one eye (0.9%) that required trabeculectomy and one (0.9%) that required vitrectomy with cataract extraction for suspected phacoanaphylactic glaucoma. Two eyes (1.8%) developed retinal detachment; both had previously been treated for retinal breaks. One eye (0.9%) developed culture-positive endophthalmitis.ConclusionsSignificant morbidity is associated with IVTA injection; clinicians should be aware when considering treatment options.

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 …

Scleral hydraulic conductivity and macromolecular diffusion in patients with uveal effusion syndrome

PURPOSE To determine whether uveal effusion syndrome (UES) is caused by altered scleral permeability to water and large molecules. METHODS Transscleral water movement was measured using surgically removed sclera clamped in a modified Ussing chamber and connected to a water column set at intraocular pressure. Sclera was also clamped between two hemichambers, and transscleral diffusion of FITC-dextrans (4.4-77 kDa) was measured with a spectrophotometer. Clinical data were prospectively collected using postal questionnaires. RESULTS Ten patients (mean age, 63 years; mean spherical equivalent, +4.7 D) had a median preoperative visual acuity of 0.20 that improved to 0.33 after surgery. Nine eyes showed visual improvement, three worsened, and two were unchanged. Histology showed disorganization of collagen fibrils, with amorphous deposits expanding the interfibrillary spaces. The mean thickness (+/-1 SD) of the excised scleral specimens was 585 +/- 309 microm, and the mean specific hydraulic conductivity was 23.9 +/- 27.5 x 10(-14) cm(2), compared with 5.8 +/- 3.9 x 10(-14) cm(2) in age-matched control specimens (P = 0.068). Three specimens had hydraulic conductivity above the 95% CI of the controls. Control eyes showed a significant reduction in diffusion coefficient (D) with age. Eyes had a mean D of 5.69 +/- 5.35 x 10(-8) cm(2) x s(-1), similar to control eyes (6.14 +/- 2.40 x 10(-8) cm(2) x s(-1), 20 kDa dextran). In one eye, the result was higher than the 95% CI of the control; in three, it was lower. CONCLUSIONS UES is not caused by reduced scleral hydraulic conductivity, which tends to be higher than expected. Reduced macromolecular diffusion may impede the normal transscleral egress of albumin with subsequent osmotic fluid retention in some, but not all eyes.

Expanding role of local anaesthesia in vitreoretinal surgery.

PurposeLocal anaesthesia (LA) is increasingly common in vitreoretinal surgery. However, younger patients often have such surgery under general anaesthesia (GA). We reanalysed the anaesthetic practice for vitreoretinal surgery in our unit over a 19-month period.MethodsA total of 1003 patients undergoing vitreoretinal surgery between August 2000 and February 2002 were studied. Type of surgery, patient pain score to anaesthesia and surgery, need for sedation and incidence of complications related to the local anaesthetic were recorded. Comparisons were made between this case series and previous data from our unit.ResultsIn total, 920/1003 (91.7%) patients had LA. Total operations comprised 418 vitrectomies, 518 retinopexies with or without vitrectomy and 67 buckling procedures. More patients under the age of 35 years had LA than previously (60.2 vs35.7%, P<0.001). In 920/920 (100%) of cases, LA was administered via intraconal injection, compared to 164/1221 (13.4%) of procedures previously. Significantly more patients under the age of 35 years required sedation (35.9%) than did older patients (19.2%). Overall, use of sedation was significantly increased since our previous study (20.2 vs7.8%). Anaesthesia and surgery were well tolerated by patients. There were no cases of orbital haemorrhage or ocular perforation. Complications included bradycardia requiring atropine 1/920 (0.1%) and chemosis 88/920 (9.6%).ConclusionsLA is well tolerated and effective even in younger patients. Sedation may well be required in younger patients and for procedures involving scleral buckling. The main indication for GA was patient preference. Despite this, such patients accounted for only 5.2% of the total.

Effect of digital image compression on screening for diabetic retinopathy

BACKGROUND/AIMS Digital imaging is widely used for diabetic retinopathy screening. The storage and transmission of digital images can be facilitated by image compression. The authors aimed to assess the effect of image compression on the accuracy of grading diabetic retinopathy. METHODS Forty nine 35 mm transparencies (17 with no retinopathy, eight with background, five with preproliferative, and 19 with proliferative retinopathy) were digitised and subjected to JPEG compression by 90%, 80%, 70%, and 0%. The 196 images were randomised and graded on a portable computer. Two masked graders assessed the images for grade of retinopathy and image quality (0–10). The sensitivity and specificity of retinopathy grading were calculated with a weighted kappa for grading agreement between levels of compression. RESULTS The sensitivity of retinopathy grading was reduced by JPEG compression. At 90%, 80%, 70%, and 0% compression the sensitivities were 0.38, 0.50, 0.65, and 0.72, respectively; the specificity results were 1.00, 1.00, 0.83, and 0.84, respectively; and the weighted kappa scores were 0.60, 0.75, 0.77, and 0.84, respectively. The quality scores for 90%, 80%, 70%, 0% compression were 2.9 (SD 1.1, 95% CI; 2.7–3.2), 4.6 (SD 1.1, 95% CI; 3.0–5.6), 5.8 (SD1.5, 95% CI 5.0–6.6), 6.3 (SD1.4, 95% CI; 5.4–7.2) (p<0.01 for each intergroup comparison). CONCLUSION The results demonstrate significant loss of sensitivity to the features of diabetic retinopathy with JPEG compression; this was compounded by the thin film transistor (TFT) screen. The authors found the quality of uncompressed images on TFT screens too poor to give grading sensitivities which reach current guidelines for diabetic retinopathy screening.

Non-communication between ophthalmologists and optometrists.

Many patients seen in the British hospital eye service are referred by high-street optometrists; and, if the optometrist is to receive feedback from the ophthalmologist, the patient should consent to disclosure of medical information. On the referral form (revised GOS 18) there is a space for this purpose. We investigated the level of communication by asking optometrists in our hospital catchment area about their use of the GOS 18 form and by examining the medical records of all new patients seen in the eye outpatient department in one month. 79 optometrists (55%) returned the questionnaire. 54 routinely used the GOS 18; and, of these, 10 said they obtained patient consent always, 23 sometimes and 21 never. 158 of 555 sets of medical notes contained an optometrists referral, 107 of them on the revised GOS 18; and patient consent had been recorded on 17 of these forms. Ophthalmologists responded to the optometrist in 2/17 (12%) cases where consent had been obtained and 15/90 (17%) where it had not. Ophthalmologists could provide much better feedback to optometrists. The GOS 18 form could be used more effectively; and there is no reason why patient consent to disclosure of medical information should not be obtained by ophthalmologists as well as by optometrists.

Outcome of intravitreal triamcinolone acetonide in postoperative cystoid macular oedema.

AimsTo assess the efficacy and safety of intravitreal triamcinolone in the treatment of postoperative cystoid macular oedema (CMO).MethodsA retrospective case series review of 21 eyes (20 patients) that had an intravitreal injection of triamcinolone 4 mg for postoperative CMO. Diagnosis was confirmed by fundus fluorescein angiography and/or optical coherence tomography in all eyes.ResultsMean age of patients was 71.1 years. CMO had developed following routine phacoemulsification cataract extraction (13 eyes), phacoemulsification cataract extraction complicated by posterior capsule tear and vitreous loss (two eyes), vitrectomy (three eyes), or planned combined phacoemulsification and vitrectomy (three eyes). Mean duration of CMO before triamcinolone injection was 4.9 months. Mean duration of follow-up was 7.4 months. Two eyes required a repeat injection. Mean logarithm of minimum angle of resolution (LogMAR) visual acuity (VA) before treatment was 0.53; at 1 month post injection, this increased significantly to 0.33 (P<0.001). Improvement in VA was maintained throughout follow-up; at 6 months or later, mean LogMAR VA was significantly better than baseline (0.33 vs 0.53, P=0.02). At the latest review, 43% of eyes had improved Snellen VA by two or more lines and 86% by one or more lines compared to baseline. The remaining 14% had reduced Snellen VA compared to baseline. In the post-injection period, 33% of eyes developed an intraocular pressure of 22 mm Hg or higher and all responded well to short-term topical agents. There were no other post-injection complications.ConclusionIntravitreal triamcinolone results in a rapid improvement in VA that may be sustained for more than 6 months.

UK survey of attitudes to local anaesthesia for vitreoretinal surgery.

Background The use of local anaesthesia (LA) for vitreoretinal (VR) surgery is growing although surgeons in the UK traditionally use general anaesthesia.Purpose To assess the use and attitudes towards local anaesthesia for VR surgery among the members of the British and Eire Association of Vitreo-retinal Surgeons (BEAVRS).Methods A questionnaire was sent to members of BEAVRS. Use of LA was assessed for the following procedures: macular hole; diabetic vitrectomy; vitrectomy; cryopexy and gas; buckling and re-buckling procedures. Attitudes of surgeons generally using LA for primary retinal detachment surgery (< 50% of cases) were compared with those generally using general anaesthesia (GA) (< 50% of cases).Results 33.6% of surgeons preferred LA for macular hole; 26.2% for diabetic vitrectomy; 23.3% for vitrectomy, cryopexy and gas; 21.4% for buckling procedures; and 9.35% for re-buckling procedures. When surgeons routinely using LA were compared with those regularly using GA they considered LA less stressful for patients and surgeon, patients tolerant to longer operations, and buckling or redo surgery no more difficult under LA. However, both groups considered surgery on young patients and teaching relatively more difficult under LA.Conclusion The use of LA may convey benefits for VR surgery and faster rehabilitation for patients. However, we identified wide variations in the use of and attitudes to LA for VR surgery in British surgeons.