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.

Surgical treatment for infarct-related ventricular septal defects. Improved early results combined with analysis of late functional status.

A total of 101 patients (mean age 64.9 years) underwent surgical correction of postinfarction ventricular septal defect at this institution over a 15-year period (1973 to 1988). The overall early mortality rate was 20.8%, although the most recent experience with 36 patients (January 1987 to October 1988) has seen this decline to 11.1%. Factors found to influence early death significantly, when analyzed univariately, were as follows: (1) site of infarction (anterior 12.1%, inferior 32.6%, p = 0.02); (2) time interval between infarction and operation (less than 1 week 34.1%, greater than 1 week 10.5%, p = 0.008); (3) cardiogenic shock (present 38.1%, absent 8.5%, p = 0.001). Nonsignificant variables included preoperative renal function, age, and concomitant coronary artery bypass, although older age (greater than 65 years) became significant when examined in a multivariate fashion. Of the 80 hospital survivors, eight were subsequently found to have a recurrent or residual defect necessitating reoperation, with survival in seven. Late follow-up is 99% complete and reveals an actuarial survival rate for 100 patients of 71.1% at 5 years (95% confidence interval 60.6 to 80.0), and 40.0% at 10 years (95% confidence interval 21.7 to 58.4). A significant recent change in policy of not using coronary angiography in patients with a ventricular septal defect caused by anterior wall infarction has not resulted in any increase in either the early mortality or in the late prevalence of angina. The functional status of 38 surviving patients has been analyzed by a graded treadmill exercise protocol, whereas left ventricular functional assessment was by nuclear scan with additional information on mitral valve function by echocardiogram. Color Doppler flow mapping has been used to determine the presence of a residual defect. Most late survivors have limited exercise tolerance related to both cardiac and noncardiac factors. Left ventricular function is moderately impaired (mean ejection fraction = 0.39). However, many patients are elderly and have adapted to their residual symptoms without significant changes in life-style.

Survey of colour contrast sensitivity in non-ophthalmic users of blue-green wavelength argon lasers.

BACKGROUND: Previous studies have shown that ophthalmologists using blue-green argon laser may suffer subtle defects in their colour vision. A reduction in colour contrast sensitivity in the tritan colour confusion axis, an early manifestation of blue cone photoreceptor injury by the high energy photons of the laser, has been demonstrated and has prompted a reappraisal of laser safety in ophthalmology. Argon laser is also frequently used in scientific research, often at higher power output and for longer periods than is used in clinical practice. The scientists operating these lasers are at risk of developing similar phototoxic retinal injury. METHODS: The colour contrast sensitivity of 18 scientists who regularly use short wavelength argon laser was investigated. RESULTS: Eye protection was infrequently used and individuals had been subjected to between 580 and 7200 hours of cumulative laser exposure during the course of their research. CONCLUSION: The use of blue-green argon laser by the scientists investigated was not associated with a significant reduction in colour contrast sensitivity.

The effect of pilocarpine on the glaucomatous visual field.

Patients with chronic open angle glaucoma are traditionally managed by medical therapy during the early stages of the disease. Pilocarpine is a well established topical agent, but suffers troublesome sequelae, the most apparent of which is pupillary constriction. This study assesses the effect of miosis (produced by one drop of 2% pilocarpine) on the static threshold perimetry of 20 subjects with chronic open angle glaucoma and documented visual field loss, using the 30-2 program of the Humphrey field analyser. Following miosis, the Statpac mean defect deteriorated by an average of -1.49 dB compared with baseline (p = 0.004). This dB deterioration is twice that reported in studies on younger normal subjects following miosis. The decrease in mean defect showed a positive correlation with the degree of pupillary constriction, the correlation being greater in those eyes with a miosed pupil diameter of 2 mm or less. There was no significant decrease in the other Statpac global indices following miosis. A parallel study using the fellow eye of the same glaucoma patients showed a high degree of intertest variability, but no significant learning or fatigue effect. We conclude that pilocarpine-induced miosis causes a significant deterioration in visual field in a population of patients with chronic open angle glaucoma: this factor should be considered when choosing therapy for glaucoma particularly in cases where field loss approaches the permitted legal minimum for driving.

Current practice of cataract extraction and anaesthesia.

A questionnaire regarding preferred methods of cataract extraction and anaesthesia was sent to 456 consultant ophthalmologists in England and Wales. Replies were received from 86% (n = 392), 83% (n = 380) having completed the questionnaire in full. The most frequently employed surgical approach was non-automated extracapsular cataract extraction. Only 2% of surgeons (n = 8) used phacoemulsification routinely and 2% (n = 7) used intracapsular extraction. Intraocular lens implantation was the standard practice of 99% of surgeons (n = 376). There has been a dramatic increase in the popularity of local anaesthesia, which was employed routinely (in more than three-quarters of their cases) by 20% of surgeons (n = 76). Retrobulbar infiltration remains the most common method of administration. Sedation was given routinely by 45% of surgeons (n = 171) when using local anaesthesia. Medical contraindications and patient preference were considered the most important reasons for selecting local anaesthesia rather than general. The exclusive use of general anaesthesia in cataract surgery appears to be diminishing.

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.

Direct ophthalmoscopy versus slit lamp biomicroscopy in diagnosis of the acute red eye.

The causes of red eye range from trivial to life-threatening, and many general practitioners are uncertain of their ability to diagnose them with the aid of an ophthalmoscope. We tested the hypothesis that, in the assessment of a patient with red eye, a doctor using a slit lamp biomicroscope would not differ in diagnostic accuracy from a doctor using a direct ophthalmoscope. A cross-over study was conducted in 98 patients newly attending an eye casualty department. 71% of diagnoses agreed exactly, and all potentially sight-threatening lesions were either diagnosed correctly or managed appropriately by doctors using an ophthalmoscope. We conclude that the initial diagnosis and management of patients with an acute red eye is not prejudiced by the lack of a slit lamp biomicroscope.

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.

Bimedial rectus recession using the anchored hang-back technique.

Hang-back recession of a rectus muscle offers several advantages over conventional techniques: a reduced risk of scleral perforation, easy intraoperative adjustment, and a convenient site for suturing to the sclera. There are also disadvantages: the muscle tends to collapse, thereby increasing the effective recession and making the result less predictable. In addition, the insertion cannot accurately be displaced upward or downward, as may be required to correct A- and V-patterns, or vertical deviations. The authors describe a modified technique, an anchored hang-back recession, and discuss the results in 60 consecutive cases of bimedial rectus recession.

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 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.

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.

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.

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.

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.