Retinal pigment epithelium transplantation: concepts, challenges, and future prospects.

The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD.

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 IL1beta -511C/T, IL6 -174C/G, IL8 -251A/T and anti-inflammatory IL10 -1082G/A cytokine polymorphisms using the 5' nuclease TaqMan(R) 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.

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

AIM: Mutation 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. METHODS: A 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. RESULTS: The 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. CONCLUSION: In 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.

Outcome of intravitreal triamcinolone acetonide in postoperative cystoid macular oedema.

AIMS: To assess the efficacy and safety of intravitreal triamcinolone in the treatment of postoperative cystoid macular oedema (CMO). METHODS: A 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. RESULTS: Mean 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. CONCLUSION: Intravitreal triamcinolone results in a rapid improvement in VA that may be sustained for more than 6 months.

An unusual maculopathy after routine cataract surgery.

AIMS: To report the presentation of apparent acute and transient vitreomacular traction causing reduction in visual acuity following routine cataract surgery. METHODS: A case series describing three patients that developed acute and transient vitreomacular traction following routine cataract surgery by experienced surgeons. No patients had any significant past medical or ophthalmic history. The patients presented shortly after surgery with reduction in visual acuity and dramatic optical coherence tomography (OCT) images suggesting vitreomacular traction. RESULTS: All three patients experienced spontaneous resolution of symptoms and clinical signs within the first few weeks after surgery. Two patients experienced continued mild metamorphopsia. CONCLUSION: To our knowledge, this is the first documented report of such cases with associated confirmation by OCT imaging.

Ocular morbidity associated with intravitreal triamcinolone acetonide.

AIM: To report on the complications associated with the use of intravitreal triamcinolone acetonide (IVTA) in a tertiary referral hospital setting. MATERIALS AND METHODS: A retrospective case series review of all IVTA injections carried out over a period of 30 months. RESULTS: One 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. CONCLUSIONS: Significant morbidity is associated with IVTA injection; clinicians should be aware when considering treatment options.

Expanding role of local anaesthesia in vitreoretinal surgery.

PURPOSE: Local 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. METHODS: A 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. RESULTS: In 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 vs 35.7%, 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 vs 7.8%). 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%). CONCLUSIONS: LA 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 video display on the grading of diabetic retinopathy.

PURPOSE: Digital images are increasingly being used in ophthalmology. These may be viewed either on thin-film transistor (TFT) or on cathode-ray tube (CRT) displays. However, there is little data showing which is superior. In this study, we compared the performance of CRT and TFT displays for grading of both compressed and uncompressed images of diabetic retinopathy. METHODS: A total of 49 35 mm transparencies of diabetic retinopathy were scanned and compressed. The images comprised 17 with no retinopathy, eight with background, five with preproliferative, and 19 with proliferative retinopathy. Four levels of compression were used: 0, 70, 80, and 90%. A total of 196 randomised images were presented to two masked graders using both TFT and CRT displays under uniform lighting conditions, 2 months apart. The grade of retinopathy was assessed. Statistical analysis of grading accuracy was performed using receiver operator characteristic curves of sensitivity and specificity and the Stuart-Maxwell test for paired, nonparametric data. RESULTS: Both displays showed high sensitivity and specificity for the detection of any retinopathy. For the specific grade of retinopathy, the CRT performed slightly better with a sensitivity of 0.80 for uncompressed images, compared with 0.75 using the TFT. Compression reduced these sensitivities to 0.73 on the CRT and 0.63 on the TFT. Grading of uncompressed images magnified to four times their original size was more accurate on the TFT. CONCLUSIONS: Grading on both displays met sensitivity and specificity criteria proposed by Diabetes UK (formerly British Diabetic Association) for screening of diabetic retinopathy. The CRT generally performed slightly better than the TFT in relation to the detection of the specific grade of retinopathy.

Affluence is not related to delay in diagnosis of Type 2 diabetes as judged by the development of diabetic retinopathy.

AIM: To determine the relationship between affluence and the presence of diabetic retinopathy at time of diagnosis of Type 2 diabetes. METHODS: Records of patients held by Southampton Retinal Screening Programme were examined. Patients (n = 1844) newly diagnosed with Type 2 diabetes and subsequently receiving photographic retinal screening within 24 months were selected. Townsend scores for social deprivation were calculated and the patients with and without retinopathy at first screening were then compared. RESULTS: No significant difference was found in the median Townsend score of those people with (-0.2, interquartile range (IQR) -3.7 to 3.8) and those without (-0.5, IQR -3.3 to 3.6) diabetic retinopathy at first screening after diagnosis of Type 2 diabetes (P = 0.6). CONCLUSION: The relative affluence of the area in which a person lives, as judged by postcode, does not appear to predict likelihood of diabetic retinopathy at diagnosis of Type 2 diabetes.

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.

Local anaesthesia for vitreoretinal surgery: an audit of patient and surgical experience.

PURPOSE: Local anaesthesia for vitreoretinal surgery is little used as these procedures are deemed to be too long and uncomfortable for patients to tolerate. In this unit anterior intraconal local anaesthesia is used for most routine surgery. We undertook an audit to ensure that surgical standards and patient acceptability were not compromised. METHODS: A prospective observational audit was performed. Audit data included: Grade of anaesthetist and surgeon; details of anaesthetic and operation; compliance of patient; operating conditions and pain scores. Anaesthesia was provided with a combined peribulbar and intraconal anaesthetic, using bicarbonate buffered lignocaine and bupivacaine 50:50 mixture. RESULTS: 135 (76%) had local anaesthesia alone, 13 (7%) had local anaesthesia with sedation and 29 (16%) had general anaesthesia. 96.4% of patients were compliant and 98.8% of operating conditions were good or excellent. The mean perioperative pain score was 0.1 (range of 0-1), 97% said they would choose local anaesthesia again. CONCLUSIONS: LA for vitreoretinal surgery is a useful and flexible method of anaesthesia, which has been shown to have excellent patient tolerance.

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 optometrist's 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.