Genotyping and functional analysis of a polymorphic (CCTTT)(n) repeat of NOS2A in diabetic retinopathy.

Accumulating evidence shows that the severity and rapidity of onset of diabetic retinopathy are influenced by genetic factors. Expression of the nitric oxide synthases is altered in the retinal vasculature in the early stages of diabetic retinopathy. We analyzed the allele distribution of a polymorphic pentanucleotide repeat within the 5' upstream promoter region of the NOS2A gene in samples of diabetic patients. In diabetic patients from Northern Ireland, the 14-repeat allele of the NOS2A marker was significantly associated with the absence of diabetic retinopathy. Carriers of this repeat had 0.21-fold the relative risk of developing diabetic retinopathy than noncarriers of this allele. They also had significantly fewer renal and cardiovascular complications. The ability of differing numbers of (CCTTT)(n) pentanucleotide repeats to induce transcription of the NOS2A gene was analyzed using a luciferase reporter gene assay in transfected colonic carcinoma cells. Interleukin 1beta (IL-1beta) induction was most effective in constructs carrying the 14-repeat allele. When cells were incubated in 25 mM glucose to mimic the diabetic state, IL-1beta induction was inhibited in all cases, but to a significantly lesser extent with the 14-repeat allele. These unique properties of the 14-repeat allele may confer selective advantages in diabetic individuals, which may delay or prevent microvascular complications of diabetes.

Dinucleotide repeat polymorphisms in EDN1 and NOS3 are not associated with severe diabetic retinopathy in type 1 or type 2 diabetes.

PURPOSE: Endothelin-1, and constitutive endothelial nitric oxide synthase, have been implicated in the pathogenesis of diabetic retinopathy. We therefore screened polymorphisms within the genes encoding these two vasoactive agents in a sample of individuals with 15 years of diabetes and no retinopathy (ETDRS level 10 or better) and those with severe retinopathy (ETDRS level 50 or worse). METHODS: PCR primers for highly polymorphic sites within the EDN1 and NOS3 genes were used to genotype individuals with type 1 or type 2 diabetes with severe or no retinopathy. Allele frequencies were compared between groups using chi-squared analysis and adjusting for multiple comparisons. RESULTS: No significant differences were observed in allele frequencies for these two markers between the patients who had retinopathy and the patients who did not. CONCLUSION: Polymorphic variability in the EDN1 and NOS3 genes does not appear to have a major impact on determining susceptibility or resistance to diabetic retinopathy.

Trends in vitreoretinal surgery at a tertiary referral centre: 1987 to 1996.

AIM: To identify trends in vitreoretinal surgery at a tertiary referral centre from 1987 to 1996. METHODS: A retrospective study of patients who had undergone vitreoretinal surgery at St Paul's Eye Unit over two 6 month periods in 1987 and 1996. Preoperative ocular status, surgery details, and outcome were collected. chi 2 and Mann-Whitney U tests were used to analyse the data. RESULTS: The two periods under study were July to December 1987 and January to June 1996. 110 operations performed during 1987 (96 patients) and 330 operations during 1996 (289 patients) were analysed. There was a fourfold rise in the number of tertiary referrals and a seven-fold rise in the number of operations performed for conditions other than rhegmatogenous retinal detachment (RRD). Increasing indications for surgery included diabetic eye disease, macular hole, dropped nucleus, endophthalmitis, and subretinal neovascular membrane. There was a rise in the proportion of patients with RRD following cataract surgery (from 19.5% to 29.5%). For both primary repair and reoperation, vitrectomy with internal tamponade was more commonly used in 1996. The anatomical success rate for primary repair changed from 76.6% to 84.7% after one operation and from 89.1% to 94.3% following additional surgery. CONCLUSIONS: This study points to a trend towards subspecialisation and tertiary referral in vitreoretinal surgery. Vitrectomy techniques are more commonly used for the primary repair of RRD and are applied to a wider spectrum of diseases.

Vitreous loss during conversion from conventional extracapsular cataract extraction to phacoemulsification.

PURPOSE: To study the outcome of vitreous loss among senior surgeons converting from conventional extracapsular cataract extraction (ECCE) to phacoemulsification. SETTING: A university teaching hospital in the United Kingdom. METHODS: A retrospective analysis of 87 planned cataract extractions performed from January 1992 to December 1996 and complicated by vitreous loss was done. Outcome measures included postoperative complication rates and visual acuity. RESULTS: During the study, vitreous loss occurred in 39 patients having ECCE and in 48 having phacoemulsification; the latter group included 8 patients with dropped nucleus. Postoperative complications included cystoid macular edema (18.7% of phaco patients, 30.8% of ECCE patients), retinal detachment (2.1% of phaco patients, 5.1% of ECCE patients), and expulsive hemorrhage (5.1% of ECCE patients). Phaco patients had higher rates of postoperative corneal edema (27.1%) than ECCE patients (12.8%) and transient intraocular pressure elevation (33.3%) versus 20.5%) but were more likely to receive posterior chamber intraocular lenses (70.8% versus 35.9%; P = .0024, chi-square test). After excluding pre-existing diseases, 83.3% of phaco patients and 67.6% of ECCE patients achieved a visual acuity of 6/12 or better. CONCLUSIONS: With careful patient selection, experienced extracapsular surgeons converting to phacoemulsification can achieve favorable results even in the presence of complications such as vitreous loss or dropped nucleus.

Delays in the diagnosis of uveal melanoma and effect on treatment.

PURPOSE: To investigate the mode of presentation of uveal melanomas, delays in their diagnosis and the effect of delayed diagnosis on treatment outcome. METHODS: An analysis was carried out of 50 consecutive patients undergoing treatment for uveal melanoma at the Ocular Oncology Service in Liverpool. The mode of presentation of the tumour, onset of symptoms and subsequent management were determined by interview at the time of treatment. RESULTS: Seventy-two per cent of patients had one or more symptoms directly attributable to the tumour. These included blurred vision (36%), photopsia (22%), visual field loss (16%), floaters (4%) and metamorphopsia (4%). Forty-two per cent of patients experienced delays in the diagnosis and treatment due to misdiagnoses such as macular degeneration and naevus or due to the lesion being missed at the initial visit. Patients who had experienced delays in diagnosis received treatment after a mean of 6.6 months compared with 4.2 weeks for those who did not experience any delay (p = 0.003). Such patients were more likely to be treated by enucleation (52% vs 17%, p = 0.008) than by an eye-conserving method such as radiotherapy or trans-scleral local resection. CONCLUSIONS: The primary aim of treatment of uveal melanoma is to reduce the risk of death from metastases and a secondary aim is to conserve the eye with as much vision as possible. This study identifies common reasons for delays in the diagnosis of uveal melanoma. While the effect of early treatment on survival remains controversial, this study shows that patients who have their tumours diagnosed promptly are more likely to be treated by an eye-conserving method than by enucleation.

Taping outpatient consultations: a survey of attitudes and responses of adult patients with ocular malignancy.

PURPOSE: To study the attitudes and responses of cancer patients to audiotaped consultations as a communication aid in an ophthalmic clinic. METHODS: Ninety-four patients attending an ocular oncology clinic were given an audiotape of their initial consultation. They were then administered a structured interview with questionnaire regarding their views on the tape when they attended an outpatient clinic for follow-up after surgery or radiotherapy. RESULTS: 91% of patients had listened to the tape at least once, often prior to their treatment or follow-up visit. Most patients had shared the tape with immediate relatives, including their spouse (58%) or other family members (45%). Of those who had listened to the tape, 94% described it as very useful or quite useful in helping them understand their condition. The majority had found it valuable in helping them understand their treatment and its side-effects, in reducing their fears and anxieties and in their emotional and psychological adjustment to their illness. Most commented on the tape as a valuable communication aid to the consultation process. CONCLUSIONS: Taping of the consultation as a method of improving communication is popular among cancer patients. The vast majority benefit greatly from being able to hear their consultation again in their own time.

Ophthalmic complications of HIV/AIDS.

As a result of improved treatment and patient survival, ophthalmic complications are now being seen with increasing frequency in AIDS, occurring in up to 75% of patients during the course of the disease. The eye may be involved by an AIDS-related microvasculopathy, which gives rise to cotton wool spots, and by opportunistic infections caused by a wide range of organisms, including cytomegalovirus, herpes simplex virus, varicella zoster, Toxoplasma gondii, Mycobacterium avium-intracellulare, Treponema pallidum, Pneumocystis carinii and various fungal agents. Opportunistic infections may be the presenting sign of disseminated infection. The eye may also be involved by neoplasms such as Kaposi's sarcoma and lymphoma, and by intracranial disease. Ocular involvement may lead to blindness if untreated and prompt ophthalmological referral is essential. This article reviews the range of ocular diseases seen in HIV and AIDS, current therapeutic options and outcome.

A comparison of the efficacy of Holmium laser sclerostomy ab externo versus trabeculectomy in the treatment of glaucoma.

We compared 15 patients who had undergone Holmium laser sclerostomy ab externo with 15 who had had trabeculectomy. In the short term, laser sclerostomy led to adequate control of intraocular pressure, but in the longer term it compared unfavourably with trabeculectomy in terms of efficacy, complications and reoperation rate. At 1 year follow-up, 8 patients in the laser group had had to undergo a second operation compared with none in the control trabeculectomy group, and 7 were still on glaucoma medication compared with 2 in the control group. Iris prolapse into the internal sclerostomy ostium within 2 months accounted for most failures, and was only partially amenable to Nd:YAG peripheral iridectomy. This common complication seems to be related to anterior chamber depth. There also appears to be a tendency for blockage of the sclerostomy with cellular or fibrinous debris. Recent literature is reviewed and modifying strategies discussed.