Novel insights into the pathophysiology of proliferative vitreoretinopathy: The role of vitreoschisis-induced vitreous cortex remnants.

PURPOSE: We previously hypothesized a causal relationship between vitreoschisis-induced vitreous cortex remnants (VCR) and the development of proliferative vitreoretinopathy (PVR). This study aims to substantiate this association through histopathological analysis of surgical specimens in support of strategies to improve therapeutic outcomes. METHODS: A descriptive, prospective, non-consecutive case series. Histopathological and immunohistochemical analyses were performed on membranes removed from the peripheral retinal surface during initial vitrectomy for primary rhegmatogenous retinal detachment (RRD) (n = 11) or recurrent retinal detachment (n = 12). The clinical aspect of the membranes ranged from loose-meshed membranes visualized with triamcinolone to more fibrotic membranes stained with trypan blue. RESULTS: Consistent with the clinical presentation, histopathological analysis revealed membranes with different area characteristics. Paucicellular lamellar collagen-rich areas, suggestive of VCR, appeared to transition to areas of increased cellularity and eventually more fibrotic areas of low cellularity. Five different area characteristics could be identified that seemed to correspond to five histopathological stages in PVR formation, with lamellar VCR collagen acting as an essential precondition: 1. Lamellar collagen, low cellularity (hyalocytes). 2. Lamellar collagen, increased cellularity (hyalocytes, glial cells). 3. Lamellar collagen, high cellularity (macrophages, glial cells, RPE-cells). 4. Early fibrosis, decreased cellularity (myofibroblasts). 5. Fibrosis, low cellularity (myofibroblasts). CONCLUSION: These findings confirm the role of VCR in preretinal PVR formation posterior to the vitreous base. We propose that the presence of VCR over the retinal surface should be qualified as a risk factor for PVR formation. Detection and adequate removal of VCR may improve the success rate of vitreoretinal surgeries.

Bilateral panuveitis following intravesical BCG immunotherapy for bladder carcinoma.

PURPOSE: To report a case of bilateral panuveitis following local treatment with Bacille Calmette-Guérin (BCG) immunotherapy for superficial bladder carcinoma. DESIGN: Case report and literature review. METHODS: A 70-year-old female presented with severe bilateral anterior chamber inflammation 5 days after intravesical BCG instillation. Despite topical steroids and mydriatics, inflammation worsened and bilateral optic nerve swelling developed. RESULTS: Oral corticosteroids settled the ocular inflammation, and optic nerve function recovered. A trial of steroid cessation caused rebound uveitis, so she remains on maintenance doses of oral corticosteroid. CONCLUSIONS: Ocular inflammations following BCG therapy for bladder cancer are rare, and little is known about the management of such cases. This is the first report of bilateral panuveitis with optic nerve edema following such treatment.

Long-term outcomes following full macular translocation surgery in neovascular age-related macular degeneration.

BACKGROUND/AIMS: Long-term data of macular translocation for choroidal neovascularisation (CNV) secondary to age-related macular degeneration is lacking. Therefore, we describe the 3-year acuity outcomes. METHODS: This is a retrospective, interventional case series consisting of 40 consecutive patients who underwent translocation between 2003 and 2008. Best-corrected visual acuity (BCVA) at the most recent follow-up visit was compared to that of the 1 year and pre-operative visits. Delayed post-operative complications were recorded, as diagnosed by clinical examination, spectral-domain optical coherence tomography, fundus autofluorescence imaging and angiography. RESULTS: The mean (range) follow-up duration was 37.6 months (range 12.4-67.4 months). Median BCVA values were 0.80, 0.70 and 0.78 log(MAR) at the baseline, 1 year and most recent visits (p=0.13). A three-line gain in BCVA was seen in 12 (30%) patients at 1 year and 10 (25%) patients at the last observation. Twenty-seven (68%) patients achieved a BCVA of 6/60 or better and six (15%) patients, 6/12 or better at the final visit. In the subset of the cohort followed for two or more years, 24 of 32 patients (75%) achieved a BCVA of 6/60 at 1 year but six of these (25%) lost two lines of BCVA thereafter due to recurrent CNV, idiopathic macular oedema, macular hole or macular pucker. Recurrent CNV developed in nine patients (23%) within the first 2 years and their final mean VA was 6/30. CONCLUSIONS: With close post-operative monitoring and early treatment of delayed complications, 25% of this cohort maintained a three-line gain in acuity at 3 years after macular translocation.

Long-term visual and microperimetry outcomes following autologous retinal pigment epithelium choroid graft for neovascular age-related macular degeneration.

BACKGROUND: To describe the 2- to 4-year visual and microperimetry outcomes of autologous retinal pigment epithelium (RPE)-choroid graft in patients with neovascular age-related macular degeneration (AMD). METHODS: In this retrospective cohort study, 12 patients with subfoveal neovascular AMD who had undergone autologous RPE-choroid graft between August 2004 and June 2005 were reviewed. Change in visual acuity (VA), contrast sensitivity (CS), fixation stability and retinal sensitivity on microperimetry after 2-3 years and the rates of late postoperative complications were examined. RESULTS: Patients were followed for 26-48 months (mean, 39). Median preoperative VA (logMAR) was 0.87 but declined to 1.43 (1 year), 1.46 (2 years) and 1.38 (3 years), P = 0.001. Median CS (logCS) was 0.75 preoperatively but declined to 0.45 at 2 years. Six patients had serial microperimetry. Fixation stability declined in 1 but improved in 2 patients. All 6 had decline in retinal sensitivity over the graft during follow up. Retinal detachment did not occur after 12 months but 8 developed epiretinal membrane, 12 had cystic retinal change over the graft and 4 developed recurrent choroidal neovascularization. However, 10 grafts retained autofluorescence signal at 18-48 months of follow up. CONCLUSIONS: Autologous RPE-choroid graft can maintain VA, stable fixation and retinal sensitivity in some patients for over 3 years. The spatial correlation between graft autofluorescence, outer retinal structures on optical coherence tomography and retinal sensitivity are consistent with photoreceptor cell rescue. However, we caution the use of this technique as there is high complication rate and delayed loss of retinal function.

A comparison of macular translocation with patch graft in neovascular age-related macular degeneration.

PURPOSE: To compare the long-term outcomes of macular translocation (MT) and autologous RPE-choroid patch graft (PG) in patients with neovascular age-related macular degeneration (AMD). METHODS: This is a retrospective review of the first 12 patients who underwent MT and the first 12 patients who underwent PG. Visual acuity (VA), contrast sensitivity (CS), clinical findings, and complications were recorded. Microperimetry and fundus imaging were reviewed. Outcome measures were the change in VA and CS over 3 years in each group and rates of complication. Microperimetry and fixation in three best cases from each group were described. RESULTS: The two groups were matched for age and VA. Median follow-up durations were 41 (MT) and 38 (PG) months. Median VA (logMAR) was maintained in the MT group: 0.90 at baseline and 0.69 at 3 years (P=0.09) whereas in the PG group, median VA declined from 0.87 to 1.38 at 3 years (P<0.001). Both surgical modalities had high rates of detachment and macular edema. Although more extensive RPE damage occurred in PG, the graft resisted growth of recurrent choroidal neovascularization toward the fovea. Near normal VA was achievable by each technique but macular sensitivity and fixation stability were superior in the MT group. CONCLUSIONS: In the present cohort, MT maintained VA for 3 years but PG did not. This outcome may be related to the differences in surgical approach, source of RPE, and choroidal perfusion. The authors recommend MT in preference to PG for treatment of patients with the second eye affected by neovascular AMD unsuitable for other treatment.

Evidence of retinal function using microperimetry following autologous retinal pigment epithelium-choroid graft in macular dystrophy.

PURPOSE: To describe the outcomes of autologous retinal pigment epithelium (RPE)-choroid graft in macular dystrophy. METHODS: In this prospective interventional case series, five patients with macular dystrophy were enrolled to undergo autologous RPE-choroid patch graft between August 2005 and January 2007. All patients received preoperative and postoperative evaluations including visual acuity, contrast sensitivity, reading ability, microperimetry, fluorescein angiography, indocyanine green angiography, fundus autofluorescence (AF) imaging, and optical coherence tomography (OCT). RESULTS: Patients were followed up for an average of 13.4 (9-23) months. Two patients gained reading acuity but only one regained visual task function after graft. This was maintained for approximately 12 months. Although there is an overall loss of visual acuity, contrast sensitivity, and reading ability, postoperative microperimetry demonstrated retinal sensitivity over the graft in all patients with maximum sensitivity, using a Goldmann size III stimulus of 200-ms duration, ranging from 12 to 20 dB. After surgery, one patient developed retinal detachment and two required cataract extraction at the time of removal of oil. ICG angiography demonstrated perfusion of the graft in four patients. With image registration, homogenous AF pattern in areas of the graft was found to be associated with retinal sensitivity. CONCLUSIONS: Autologous RPE-choroid graft can be performed in patients with macular dystrophy. Although microperimetry showed evidence of retinal function over a perfused and autofluorescent graft, the overall loss of visual acuity and reading ability raises concerns over the use of this novel surgical technique in these patients.

Autologous transplantation of the retinal pigment epithelium and choroid in the treatment of neovascular age-related macular degeneration.

PURPOSE: To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). DESIGN: Prospective interventional cohort study. PARTICIPANTS: Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had <6 months of acute visual loss owing to subfoveal neovascular AMD and were ineligible for photodynamic therapy. METHODS: Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch's membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector. MAIN OUTCOME MEASURES: Six months after surgery, successful transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft. RESULTS: Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could also be genetically modified outside the eye with a viral vector applied within the time frame of the operation. CONCLUSIONS: Autologous RPE transplantation can in principle restore vision in neovascular AMD, but surgical complications remain high. The possibility for ex vivo gene transfer to the free graft of RPE may widen the scope of this procedure to include gene therapy or adjunctive molecular treatments for AMD.