Gurmit S. Uppal

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).

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.

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.

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.

New algorithm for assessing patient suitability for macular translocation surgery

Purpose:  We propose a case selection algorithm to assess suitability for macular translocation for subfoveal neovascular membrane (CNV) secondary to age‐related macular degeneration. The algorithm is based on preoperative assessment of residual foveal function, as assessed by a slit‐lamp fixation task and duration of visual loss, in patients with poor acuity. We validate our slit‐lamp fixation task against an objective analysis (Nidek MP‐1 Microperimetry) and proceed to examine surgical outcomes as selected by the algorithm.

Clinicopathological case series of four patients with inherited macular disease

PURPOSE To correlate the phenotype of four patients with inherited macular disease with the immunohistopathology of retinal tissue collected at the time of retinal pigment epithelium (RPE)-choroidal transplantation. METHODS A clinicopathologic case series describing the phenotype of four patients, including confocal immunohistochemistry and electron microscopy (EM), and the results of genetic testing. RESULTS In Case 1, electrophysiology showed only macular dysfunction. Confocal microscopy revealed minor abnormalities. EM showed abnormal cone inner segments with swollen mitochondria. In case 2 (R172W mutation in RDS), electrophysiology demonstrated generalized cone system dysfunction with severe macular involvement. Peripherin labeling of outer segments was nonuniform, and EM showed discs arranged in whorllike structures. Case 3 showed severe central macular dysfunction on multifocal electroretinogram (ERG). Peripherin staining was irregular and disorganized. EM revealed abnormal inner segment morphology, particularly in rods, and disorganized irregular outer segments. Case 4 had localized central macular dysfunction on multifocal ERG. Confocal microscopy was grossly normal, with evidence of early redistribution of cone opsin to the inner segment. EM showed variable rod morphology and normal cones. CONCLUSIONS RPE transplantation provides a unique opportunity to gain insight into retinal disorders by enabling phenotypic correlation with the immunohistopathology of retinal tissue collected during surgery.

Assessment of Reading Behavior with an Infrared Eye Tracker after 360° Macular Translocation for Age-Related Macular Degeneration

PURPOSE. Macular translocation (MT360) is complex surgery used to restore reading in exudative age-related macular degeneration (AMD). MT360 involves retinal rotation and subsequent oculomotor globe counterrotation and is not without significant surgical risk. This study attempts to gauge the optimal potential of MT360 in restoring reading ability and describe the quality and extent of recovery. METHODS. The six best outcomes were examined from a consecutive series of 23 MT360 cases. Reading behavior and fixation characteristics were examined with an infrared eye tracker. Results were compared to age-matched normal subjects and patients with untreated exudative and nonexudative AMD. Retinal sensitivity was examined with microperimetry to establish threshold visual function. RESULTS. MT360 produced significant improvements in visual function over untreated disease and approximated normal function for reading speed and fixation quality. Relative to the comparative groups, eye tracking revealed the MT360 cohort generated a greater number of horizontal and vertical saccades, of longer latency and reduced velocity. In contrast, saccadic behavior when reading (forward and regressive saccades) closely matched normal function. Microperimetry revealed a reduction in the central scotoma with three patients recovering normal foveal sensitivity. CONCLUSIONS. Near normal reading function is recovered despite profound surgical disruption to the anatomy (retinal/oculomotor). MT360 restores foveal function sufficient to produce a single stable locus of fixation, with marked reduction of the central scotoma. Despite the limitations on saccadic function, the quality of reading saccadic behavior is maintained with good reading ability. Oculomotor surgery appears not to limit reading ability, and the results of retinal surgery approximate normal macular function.

Adaptive Optics Imaging Shows Rescue of Macula Cone Photoreceptors

Advanced age-related macular degeneration and inherited macular diseases remain largely untreatable. Clinical trials using stem cell transplantation have recently commenced and mark a further step in introducing cellular therapy for these diseases. Earlier techniques such as macular translocation and autologous retinal pigment epithelium (RPE), namely, choroidal transplantation demonstrated rescue of visual function in severe neovascular age-related macular degeneration. These studies aimed at long-term rescue of functional photoreceptors and macular anatomy. In the past, there has not been a way to demonstrate objectively the extent of rescue and survival of individual cone photoreceptors following interventions. Rescue was implied by functional improvement in visual acuity, retinal sensitivity by microperimetry and the integrity of the photoreceptor inner/outer segment layer on optical coherence tomography (OCT) scans.The emergenceof high-resolution adaptive optics (AO) retinal imaging system in 1996 made it possible to image the human retina directly at a cellular level in vivo. Recently, AO retinal imaging has been used to study the cone photoreceptors in macular diseases. We used an AO camera to image patients who have undergonemacular translocation, a form of indirect RPE transplantation, to study the level of photoreceptor rescue and demonstrate the longevity of rescue of cone function and structure. The study protocol was approved by the local Research Ethics Committee andcompliedwith the tenets of theDeclaration ofHelsinki. Three female patients aged 67, 76, and 82 years, who had previously (>5 years) undergone macula translocation surgery for neovascular age-related macular degeneration were recruited from the Moorfields’ vitreoretinal clinic. The best-corrected visual acuity was assessed with a modified Early Treatment Diabetic Retinopathy Study distance visual acuity chart at 4 meters. All patients underwent spectral domain OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Horizontal volume scans and infrared fundus images were used as a reference tomark the location of the area ofhealthy anddiseased retina. An AO en face reflectance imaging system (rtx1, Imagine Eyes, Orsay, France) with infrared flood illumination (wavelength, 850 nm) was used to image 4!4 degree areas of the macular cone photoreceptor layer through a dilated pupil. Retinal sensitivity was determined using microperimetry (MP; Nidek MP-1, Padova, Italy). Fixation was tested with a 1 degree cross-fixation target using a 200-ms duration Goldmann III stimulus. Stimulus intensity ranged over a 20-point logarithmic scale from 0 to 20 dB (400e4 asb). An automated 4-2 staircase threshold test strategy was used over a preselected 76-point grid area centered over their fovea. Cone photoreceptor images were registered with color fundus, infraredþOCTandMPinAdobePhotoshop (CS5,version12.0,Adobe Systems Inc, San Jose, CA) for analysis. Cone photoreceptors in the images were described by their presence and by the pattern of distribution. Manual cone counting was performed on a retinal area of 50!50mm size using the image-processing programme, ImageJ (National Institutes of Health, Bethesda, MD). The area chosen was close to fixation, along either the horizontal or vertical meridian through the fovea. Subjects attainedandmaintainedbest-correctedvisual acuityof0.04, 0.20, and 0.20 logarithm of the minimum angle of resolution, respectively, at 6, 7, and 8 years postoperative. The presence of cones, inner/ outer segment layer, and RPE layer were clearly noted at the new position of the translocatedmacula in all the 3 patients (Figures 1B, C, 2B, C, and3B,C; available at http://aaojournal.org). In thediseased areas, the retinal architecture and anatomy is disrupted with loss of the inner/outer segment and RPE layers (Figs 1D, 2D, and 3D; available at http://aaojournal.org).Coneswere present throughout in cases 1 and3, and focally at the fovea and superior to the fovea in case 2. The cone photoreceptor density for cases 1, 2, and 3 at an eccentricity of 0.18, 0.21, and 0.24mm from the fovea were 22.8!10, 12.8!10, and 13.2!10 cones/mm, respectively. The correspondingMP retinal sensitivities for these 3 cone density sampled areas were 14, 10, and 13 dB, respectively. Good visual function was noted throughout the healthy areas in cases 1, 2, and 3 with good retinal sensitivity on MP. No sensitivity was seen in the old diseased area (Figures 1A, 2A, and 3A; available at http://aaojournal.org). The success of cellular therapies for macular diseases will ultimately depend on the extent and longevity of rescue of photoreceptors. In this study, we have demonstrated that it is possible to image the rescued photoreceptors 6 to 8 years after treatment. To quantify the extent of photoreceptor rescue we compared the cone photoreceptor densities of the 3 cases with appropriate, published, age-matched normative data at equivalent eccentricities. For cases 1, 2, and 3 the paired cone counts and age matched normals were 22.8!10 and 52.6#4.4!10; 12.8!10, and 46.5 to 50.2#2.1!10; and 13.2!10 and 46.5 to 50.2#2.1!10 cones/ mm, respectively. This results in cone densities of approximately 2.3 times less for case 1 and 3.5 to 3.8 times less for cases 2 and 3, but still consistent with acuities of 0.04, 0.20, and 0.20 logarithm of the minimum angle of resolution, respectively. These counts show the rescue of photoreceptors for significant lengths of time, but at reduced levels. Being able to quantify the actual rescue of photoreceptors and correlating this with function for future cellular therapies will be crucial in defining minimal levels of useful rescue. This observational case series demonstrates survival of cone photoreceptors, using in vivo AO retinal imaging in cases of indirect RPE transplantation inmacular disease. It suggests that cone imagingmay be useful for monitoring future therapies and quantifying photoreceptor rescue relative to function. Given the recent onset of clinical trials in cellular therapies formacular disease, it is timely to show that this typeof imaging is feasible and provides useful information about outcomes.

Bacille Calmette-Guérin and Ocular Inflammations

2 with a PSA level 4 ng/mL. We have not recommended routine biopsy unless the levels have been 10 ng/mL. Lee et al reported similar findings, backed by a biopsy emonstration of benign prostatic hyperplasia in a Koean study of 707 men. Pinsky et al, in a prostate cancer screening study, showed that the prostate volume had an independent correlation with the PSA level, irrespective of the detection of malignancy. These findings are, in a way, diametrically opposite the results of the present study and others that have advocated biopsy for patients with lower PSA levels. Conflicting reports on the importance of an elevated PSA level (lower values supporting malignancy and higher values in benign high-volume prostates) inform us that PSA measurement, although a sensitive and popular tool in the screening of prostate cancer, still needs refinement to be considered an ideal marker, owing to its low positive or negative predictive value. In our attempt to detect clinically and radiologically unapparent prostate cancer using a marker that has yet to prove its specificity, it is important that we do not end up lauding ourselves for “successfully” treating a disease that might never have surfaced during the patient’s lifetime.