Scleral-fixated intraocular lens implants-evolution of surgical techniques and future developments.

Varied options are available for the implantation of secondary intraocular lens implants in the absence of zonular or capsular support. Loss of the capsule can occur in the context of complicated cataract surgery, trauma or inherited conditions such as Marfan syndrome or pseudoexfoliation. Approaches to overcome this include optical measures such as the use of spectacles or contact lenses, and surgical therapy incorporating the use of anterior chamber, iris-fixated or scleral-fixated lenses. Surgical techniques to implant scleral-fixated lenses have undergone various modifications, since the first publication of sutured intrascleral fixation described in the 1980s. However, despite the advances in surgical techniques, studies are limited either by their retrospective nature, small sample size and most importantly small duration of follow-up. This comprehensive review aims to amalgamate the evolution of various surgical techniques with regards to intrascleral lens fixation and suggests areas for future development.

Silicone oil versus gas tamponade for giant retinal tear-associated fovea-sparing retinal detachment: a comparison of outcome.

PurposeSilicone oil is the most common choice of tamponade agent used when managing a giant retinal tear (GRT). Concern exists regarding its potential detrimental effect on vision. We herein report on visual and surgical outcomes of all patients treated at Moorfields Eye Hospital for a GRT over a five year period. We further analysed a subgroup of fovea-sparing retinal detachments (RD) treated by pars plana vitrectomy (PPV) with either silicone oil or gas tamponade.MethodsRetrospective comparative, non-randomised, cross-sectional review of patients with a new diagnosis of GRT from 1 September 2005 to 31 August 2010ResultsOne hundred twenty four eyes of 118 patients were identified with mean age of 45.5 years and median follow-up of 24 months. Subgroup analysis of fovea-sparing RDs (Silicone Oil n=49, Gas n=15) revealed visual loss (≥2 Snellen Lines of vision) in 49.0% (n=24) of patients managed with oil compared to 13.3% (n=2) of gas patients (P=0.019). In all, 73.3% (n=11) in the gas group achieved a final vision of 6/12 or better, compared to 36.7% (n=18) in the oil group (P=0.031). No difference was observed in eventual or primary anatomical success rate (100 vs 93.9%, and 66.7 vs 79.6%, gas vs oil, respectively, (P>0.1)). Postoperative complications were absent in 66.7% (n=10) of gas patients compared with 14.3% (n=7) of oil patients (P=0.002). Multiple variable linear regression determined tamponade choice as the only variable predictive of final visual acuity (P=0.046).ConclusionEyes with fovea-sparing GRT-related RDs managed with gas achieved a better visual outcome with fewer postoperative complications and no significant difference in anatomical success. A multicentre approach to investigate this further is advised.

Ranibizumab pretreatment in diabetic vitrectomy: a pilot randomised controlled trial (the RaDiVit study).

PurposeOur aim was to evaluate the impact of intravitreal ranibizumab pretreatment on the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy. The objective was to determine the feasibility of a subsequent definitive trial and estimate the effect size and variability of the outcome measure.Patients and methodsWe performed a pilot randomised double-masked single-centre clinical trial in 30 participants with tractional retinal detachment associated with proliferative diabetic retinopathy. Seven days prior to vitrectomy surgery, participants were randomly allocated to receive either intravitreal ranibizumab (Lucentis, Novartis Pharmaceuticals UK Ltd, Frimley, UK) or subconjunctival saline (control). The primary outcome was best-corrected visual acuity 12 weeks following surgery.ResultsAt 12 weeks, the mean (SD) visual acuity was 46.7 (25) ETDRS letters in the control group and 52.6 (21) letters in the ranibizumab group. Mean visual acuity improved by 14 (31) letters in the control group and by 24 (27) letters in the ranibizumab group. We found no difference in the progression of tractional retinal detachment prior to surgery, the duration of surgery, or its technical difficulty. Vitreous cavity haemorrhage persisted at 12 weeks in two of the control group but none of the ranibizumab group.ConclusionRanibizumab pretreatment may improve the outcome of vitrectomy surgery for advanced proliferative diabetic retinopathy by reducing the extent of post-operative vitreous cavity haemorrhage. However, the effect size appears to be modest; we calculate that a definitive study to establish a minimally important difference of 5.9 letters at a significance level of P<0.05 would require 348 subjects in each arm.

Müller glia as an important source of cytokines and inflammatory factors present in the gliotic retina during proliferative vitreoretinopathy.

Retinal gliosis is characterized by biochemical and physiological changes that often lead to Müller glia proliferation and hypertrophy and is a feature of many neuro-degenerative and inflammatory diseases such as proliferative vitreoretinopathy (PVR). Although Müller glia are known to release inflammatory factors and cytokines, it is not clear whether cytokine production by these cells mirrors the pattern of factors present in the gliotic retina. Lysates from normal cadaveric retina and gliotic retinal specimens from patients undergoing retinectomy for treatment of PVR, the Müller cell line MIO-M1 and four human Müller glial cell preparations isolated from normal retina were examined for their expression of cytokines and inflammatory factors using semi-quantitative dot blot antibody arrays and quantitative arrays. Comparative analysis of the expression of inflammatory factors showed that in comparison with normal retina, gliotic retina exhibited greater than twofold increase in 24/102 factors examined by semiquantitative arrays, and a significant increase in 19 out of 27 factors assessed by quantitative methods (P < 0.05 to P < 0.001). It was observed that with the exception of some chemotactic factors, the majority of cytokines and inflammatory factors were produced by Müller glia in vitro and included G-CSF, MCP-1, PDGF-bb, RANTES, VEGF, and TGFß2. These results showed that a large number of inflammatory factors expressed by Müller glia in vitro are upregulated in the gliotic retina, suggesting that targeting the production of inflammatory factors by Müller glia may constitute a valid approach to prevent neural damage during retinal gliosis and this merits further investigations.

The incidence of unexplained visual loss following removal of silicone oil.

PURPOSE: To assess the incidence and clinical features of unexpected visual loss after removal of silicone oil (ROSO). PATIENTS AND METHODS: A retrospective cross-sectional observational study of 421 consecutive eyes, which underwent silicone oil removal at one institution over a 2-year period. RESULTS: Fourteen (3.3%) patients, (12 male, mean age of 53.1 years) suffered unexplained visual loss. In these eyes, the mean duration of silicone oil fill was 141 days (range 76-218). The mean loss of visual acuity was 3.7 (range 2-6) Snellen lines (SL) at 1 month, 3.5 (2-6) SL at 3 months and 2.91 (0-6) SL at 6 months. The change from preoperative visual acuity was statistically significant at all visits (P=0.02). Subgroup analysis of 20 fovea-sparing giant retinal tear (GRT) detachments, observed 10 (50%) cases of visual loss after ROSO. Electrodiagnostic testing suggested predominantly macular dysfunction, with optic nerve involvement in one case. Five of the 14 cases had variable recovery of vision. CONCLUSION: There is a 3.3% overall incidence of visual loss following ROSO with a high rate (50%) observed in maculae on GRT detachments. Although recovery of visual acuity is seen in a minority of cases, visual loss after ROSO remains a serious and unexplained concern for vitreoretinal surgeons.

Genome-wide association studies: applications and insights gained in Ophthalmology.

Genome-wide association studies (GWAS) use high-throughput genotyping technologies to genotype thousands of single-nucleotide polymorphisms (SNPs) and relate them to the development of clinical and quantitative traits. Their use has been highly successful in the field of ophthalmology, and since the advent of GWAS in 2005, many genes not previously suspected of having a role in disease have been identified and the findings replicated. We conducted an extensive literature review and describe the concept, design, advantages, and limitations of GWAS and provide a detailed description of the applications and discoveries of GWAS in the field of eye disease to date. There have been many novel findings revealing previously unknown biological insights in a diverse range of common ocular conditions. GWAS have been a highly successful modality for investigating the pathogenesis of a wide variety of ophthalmic conditions. The insights gained into the pathogenesis of disease provide not only a better understanding of underlying disease mechanism but also offer a rationale for targeted treatment and preventative strategies. Expansive international collaboration and standardised phenotyping will permit the continued success of this investigative technique.

Surgical outcome and risk stratification for primary retinal detachment repair: results from the Scottish Retinal Detachment study.

OBJECTIVES: To report the early surgical outcome, risk of failure and predictive value of rhegmatogenous retinal detachment (RRD) classification based on all participants in the Scottish Retinal Detachment study. METHODS: Over 2 years, all incident cases of RRD in Scotland were approached for recruitment. Early postoperative success was defined as an attached retina following one procedure with a minimum follow-up of 6-8 weeks. Using a regression model, the influence of clinical factors on the failure risk was estimated and the sensitivity and specificity of the Royal College of Ophthalmologists (RCOphth) grading for RRD and the vitrectomy in retinal detachment stratification risk formula (VR-SRF) in predicting operative failure were assessed. RESULTS: Primary outcome data were available for 86.2% (975/1130) of patients. The overall primary success rate was 80.8% (95% CI 78.1 to 83.3%). The presence of preoperative proliferative vitreoretinopathy of any degree and each additional clock hour of detachment increased the risk of failure by an OR of 2.4 and 1.13 respectively (p<0.05). A specificity of >95% in predicting early surgical failure was noted for highly complex RRDs according to the VR-SRF formula and the RCOphth classification. CONCLUSIONS: Consistent with previous series, the overall early success rate of RRD repair was 80% after one operation. The type of surgical repair did not influence overall success rates. Significant predictors of failure are the presence of preoperative proliferative vitreoretinopathy of any grade and the extent of detachment. The analytical value of current classification systems in predicting failure is most useful in complex RRDs.

The fellow eye in retinal detachment: findings from the Scottish Retinal Detachment Study.

AIM: To characterise the predisposing pathology and clinical features in the fellow eyes of patients recruited as part of the Scottish Retinal Detachment Study. METHODS: The Scottish Retinal Detachment Study was a 2-year prospectively recruited population-based epidemiology study that sought to recruit all incident cases of primary rhegmatogenous retinal detachment (RRD) in Scotland. RESULTS: A total of 1202 incident cases of primary RRD were recruited in Scotland, over a 2-year period and in 94% (1130 cases) detailed data on the clinical features of fellow eyes with RRD were available. Full-thickness retinal breaks were found in 8.4% (95/1130) of fellow eyes on presentation. Lattice degeneration was present in 14.5% (164/1130) of fellow eyes. Thirteen per cent (148/1130) of affected fellow eyes had a best corrected visual acuity of 6/18 or worse with previous RRD, the second most common cause of poor vision. Overall, 7.3% (88/1202) of cases had RRD in both eyes; 60% of cases with consecutive bilateral RRD presented before the macula were affected. CONCLUSIONS: Rhegmatogenous pathology in the fellow eye represents an important threat to vision. Fellow-eye detachments are more common in pseudophakic individuals and those with a more myopic refractive error. Fellow-eye RRD has a greater likelihood of prompt presentation.

Retinal detachment repair by vitrectomy: simplified formulae to estimate the risk of failure.

AIM: Devise simplified formulae, using preoperative clinical data, to give risk estimates of (1) failure and (2) proliferative vitreoretinpathy (PVR) following primary retinal detachment repair by vitrectomy. METHODS: 641 patients were analysed as part of an RCT investigating use of 5-fluorouracil and low-molecular-weight heparin. Treatment status had no effect on success rates and did not therefore form part of the analyses. Preoperative risk factors for surgical failure and for PVR within 6 months of retinal detachment surgery were identified, and a multiple variable logistic regression model developed. Further analyses were performed to devise a simple points system to produce risk estimates of failure. RESULTS: Three risk factors were related to failure-previous lens extraction (p=0.046), grade C PVR (p=0.039) and extent of detachment (p<0.001). Three risk factors were also related to failure due to PVR-vitreous haemorrhage (p=0.088), grade C PVR (p=0.044) and extent of detachment (p<0.001). There was good agreement between risk estimates produced by the points system and those calculated directly using a multivariate regression model. The points-system model gave an area under the receiver operating characteristic curve of 0.658. The receiver operating characteristic curve for the PVR model gave an area under the curve of 0.8399 suggesting greater diagnostic value. CONCLUSIONS: A simple points system may be used as a clinical guide to identify patients at higher risk of failure following retinal detachment repair by vitrectomy. This may help clinicians select appropriate surgical approaches and stratify cases in research and surgical training.

SNP mistyping in genotyping arrays--an important cause of spurious association in case-control studies.

Using genome-wide association studies to identify genetic variants contributing to disease has been highly successful with many novel genetic predispositions identified and biological pathways revealed. Several pitfalls for spurious association or non-replication have been highlighted: from population structure, automated genotype scoring for cases and controls, to age-varying association. We describe an important yet unreported source of bias in case-control studies due to variations in chip technology between different commercial array releases. As cases are commonly genotyped with newer arrays and freely available control resources are frequently used for comparison, there exists an important potential for false associations which are robust to standard quality control and replication design.

The epidemiology of rhegmatogenous retinal detachment: geographical variation and clinical associations.

AIMS/BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition. Obtaining an accurate estimate of RRD incidence in the population is essential in understanding the healthcare burden related to this disorder. METHODS: A systematic review of all population-based epidemiology studies of RRD published between January 1970 and January 2009 from Medline database searches was performed. RESULTS: RRD incidence demonstrates significant geographical variation and its incidence has been reported to be between 6.3 and 17.9 per 100,000 population. For studies with a sample size >300 the median annual incidence per 100,000 population was 10.5 (IQR 8.1-13.2) and the mean proportion of bilateral RRD was 7.26%. Overall, the mean prevalence of lattice degeneration was 45.7+/-20.3% and myopia was 47.28+/-12.59%. CONCLUSIONS: Estimates of RRD incidence have varied threefold, but inclusion criteria and other design features have differed across studies making direct comparisons difficult. The overall incidence of RRD is not yet well established: more incidence studies of adequate methodology are needed to explore temporal changes in incidence. RRD incidence varies with ethnicity and is strongly associated with increasing age, myopia and certain vitreo-retinal degenerations. Due to changes in cataract surgery trends, the proportion of pseudophakic RRD presenting to specialised centres appears to be increasing.

Retinal detachment in Scotland is associated with affluence.

AIM: Socio-economic deprivation plays a major role in health and disease, but its role in retinal detachment has not been studied. Data from the Scottish Retinal Detachment Study were used to investigate any association between retinal detachment, macular status at presentation and deprivation. METHODS: Prospective multicentre population-based observational study. Data were collected on all patients with primary retinal detachment presenting in Scotland between 1 November 2007 and 31 October 2008. Every patient was allocated a validated deprivation ranking according to their postcodes based on the Scottish Index of Multiple Deprivation (SIMD), which takes into account income, employment, health, education, housing, geographic accessibility and crime in 6505 postcode-based datazones. The patients were divided into four quartiles according to their SIMD ranking. RESULTS: 572 patients were included. The annual incidence of detachment declined from 15.4/100,000 in the most affluent quartile to 13.6/100,000 in the second, 9.3/100,000 in the third and 6.9/100,000 in the most deprived (chi(2) for trend = 50.2, p<0.0001). The trend was more marked for men than for women but was present in both sexes. There were no differences in the rate of macula-off detachments or the number of quadrants detached. Rates of pseudophakic and myopic detachment were evenly distributed across all quartiles. CONCLUSIONS: Retinal detachment appears to be associated with affluence. This has not been previously reported and may be partly responsible for the variation in estimates of the incidence of retinal detachment. It may also have implications for service planning. The reason for this association is unknown.

Histological analysis of retinas sampled during translocation surgery: a comparison with normal and transplantation retinas.

AIMS: To carry out a histopathological analysis of retinal specimens of patients undergoing translocation surgery for age-related macular degeneration (ARMD). METHODS: A histopathological analysis, using confocal microscopy, was performed on six retinal specimens. Results were compared with those from two further retinal specimens, collected during RPE transplantation, to control for the effects of vitrectomy and ARMD. In addition, a third control specimen from a cadaver with no history of ophthalmic disease was also analysed. RESULTS: In the translocation specimens, rods and cones were relatively well preserved but showed reduced density and outer segment length. In four specimens, there were focal areas of rod opsin redistribution to the inner segment, but this was not observed in the controls. Staining with calbindin was decreased in cones compared with controls but normal in horizontal and amacrine cells. Rod bipolar cells were mildly disorganised, and in one there was evidence of neurite sprouting. Glial fibrillar acidic protein was raised in both translocation and transplantation retinae but not in the cadaver control. CONCLUSIONS: In this study, there was little evidence of cellular injury following iatrogenic detachment; however, the rate of PVR following translocation surgery infers that cellular events set in motion may continue despite early reattachment.

Cataract extraction after retinal detachment repair by vitrectomy: visual outcome and complications.

AIMS: To determine the intraoperative and postoperative complications and visual outcome of eyes undergoing cataract extraction after previous retinal detachment repair by pars plana vitrectomy (PPV). METHODS: Retrospective analysis of 72 patients who had cataract extraction by phacoemulsification having had retinal detachment repair by vitrectomy and internal tamponade. RESULTS: Best-corrected visual acuity (BCVA) had improved in 53 (74%) of eyes at 3 weeks after cataract surgery and 65 (90%) at final follow-up. Fifty-three eyes (74%) attained 6/12 visual acuity at final follow-up compared with 19 (26%) eyes with a preoperative vision better than 6/12. There was a significant improvement in BCVA after cataract extraction (P<0.001). Poor vision was usually related to retinal comorbidity.Intraoperative events occurred in nine eyes (12.5%) including capsulorrhexis tears, zonular dehiscence and vitreous loss. Postoperative events occurred in 15 eyes (20.8%). Retinal re-detachment occurred in four eyes (5.6%). CONCLUSIONS: Cataract extraction after retinal detachment surgery by vitrectomy generally results in a significant visual improvement, however, there is an increased intraoperative and postoperative complication rate. The risk of retinal re-detachment may previously have been underestimated.

Comparison of macular hole size measured by optical coherence tomography, digital photography, and clinical examination.

AIM: To report on the agreement of macular hole size as measured using optical coherence tomography (OCT), Topcon digital photography, and surgeon estimate on clinical examination. METHODS: Observational cohort series of patients who underwent macular hole surgery over an 18-month period. Patients had OCT scan and digital fundus photographs preoperatively. At operation the surgeon estimated the size of macular hole. The agreement between methods was assessed using the technique described by Bland and Altman. RESULTS: There was good repeatability of photographic and OCT assessment and no evidence of systematic bias between repeated macular hole measurement by digital photography (P=0.36) or by OCT (P=0.58). There was evidence of systematic bias between photographic and surgeon measurements (P<0.001), and between OCT and surgeon (P<0.001) with photographic and OCT assessment being greater. There was also evidence of bias between OCT and photographic measurements with photographic measurement tending to be greater than the OCT measurement for smaller holes and lower for larger holes (P=0.02). CONCLUSIONS: OCT and Topcon digital photography have good repeatability for measurement of macular hole size. Both these methods measured larger hole sizes compared to surgeon estimate. Digital photography and OCT methods did not agree.

Randomized controlled trial of combined 5-Fluorouracil and low-molecular-weight heparin in the management of unselected rhegmatogenous retinal detachments undergoing primary vitrectomy.

OBJECTIVE: To determine the efficacy of a combination of 5-fluorouracil (5FU) and low-molecular-weight heparin (LMWH) in the treatment of unselected rhegmatogenous retinal detachment (RRD) undergoing primary vitrectomy. DESIGN: Double-masked, prospective, randomized, placebo-controlled clinical trial. PARTICIPANTS: Six hundred forty-one patients presenting with primary RRD were recruited from 2 specialized vitreoretinal units-Moorfields Eye Hospital, London (n = 553) and St. Pauls Eye Unit, Liverpool (n = 88). INTERVENTION: All patients underwent primary vitrectomy and gas endotamponade. Adjuvant therapy in the treatment group consisted of 5 IU/ml LMWH and 200 mug/ml 5FU added to the perioperative infusion fluid. MAIN OUTCOME MEASURES: The primary outcome measure was retinal reattachment after primary vitrectomy without any reoperations at 6 months. Secondary outcome measures recorded at 6 months were the occurrence and grade of proliferative vitreoretinopathy (PVR), best-corrected visual acuity in logarithm of the minimum angle of resolution, intraocular pressure (mmHg), corneal clarity, and complications. RESULTS: The overall primary success rate was 84.4%; in the treatment group, the primary success rate was 82.3% compared with 86.8% in the placebo group (P = 0.12). At 6 months, the final complete anatomical reattachment rate was 97.9% in both treatment and placebo groups. The number of patients who failed due to the development of PVR was not statistically significant, 23 in the treatment group (7.0%) and 14 in the placebo group (4.9%) (P = 0.309). There was no significant difference in the mean visual acuity at 6 months in the placebo group (0.48) versus the treatment group (0.53; P = 0.072). The visual acuity at 6 months of patients presenting with a macula-sparing retinal detachment was significantly worse in the treatment group (P = 0.0091). There was no significant difference between the 2 groups in patients who presented with a macula involving retinal detachment (P = 0.896). CONCLUSIONS: Primary vitrectomy has a high anatomic and visual success rate for RRD. Adjuvant therapy with 5FU and LMWH does not improve the anatomic or visual success rate of unselected primary retinal detachments undergoing vitrectomy. After adjuvant therapy, a worse visual outcome was observed in patients presenting with macula-sparing retinal detachments. A combination of 5FU and LMWH should not be used routinely for primary RRD surgery.

The effect of pars plana vitrectomy on cystoid macular oedema associated with chronic uveitis: a randomised, controlled pilot study.

AIM: To evaluate the efficacy of pars plana vitrectomy (PPV) in the management of chronic uveitic cystoid macular oedema (CMO). METHODS: A prospective, interventional, randomised, controlled, pilot study. 23 eyes of 23 patients with CMO secondary to chronic intermediate or posterior uveitis unresponsive to medical treatment were randomised into a surgical (group S) or medical group (group M). 12 patients in group S underwent PPV as opposed to 11 patients in group M who received systemic corticosteroid and/or immunosuppressive treatment during the study period. The primary outcome measures of the study were change in visual acuity and angiographic appearance of CMO at 6 months. RESULTS: Mean visual acuity in group S improved significantly from 1.0 (0.62) at baseline to 0.55 (0.29) at 6 months following vitrectomy (p = 0.011), with five (42%) eyes reaching vision of 20/40 or better. Conversely, mean visual acuity in group M improved only marginally by 0.03 (0.27) (p = 0.785). CMO after vitrectomy was angiographically improved in four (33%) eyes, remained unchanged in seven (58%) eyes, and deteriorated in one (8%) eye. In the medical group, fluorescein leakage decreased in one eye, did not alter in four eyes, and deteriorated in two eyes. CONCLUSION: PPV for macular oedema secondary to chronic uveitis despite angiographic improvement in only one third of the patients, seems to have a significant beneficial effect on visual function. This study provides enough evidence to justify a large scale trial which would define the role of vitrectomy in uveitic macular oedema.