Diabetic Macular Oedema Guidelines: An Australian Perspective.

The number of people living with diabetes is expected to rise to 578 million by 2030 and to 700 million by 2045, exacting a severe socioeconomic burden on healthcare systems around the globe. This is also reflected in the increasing numbers of people with ocular complications of diabetes (namely, diabetic macular oedema (DMO) and diabetic retinopathy (DR)). In one study examining the global prevalence of DR, 35% of people with diabetes had some form of DR, 7% had PDR, 7% had DMO, and 10% were affected by these vision-threatening stages. In many regions of the world (Australia included), DR is one of the top three leading causes of vision loss amongst working age adults (20-74 years). In the management of DMO, the landmark ETDRS study demonstrated that moderate visual loss, defined as doubling of the visual angle, can be reduced by 50% or more by focal/grid laser photocoagulation. However, over the last 20 years, antivascular endothelial growth factor (VEGF) and corticosteroid therapies have emerged as alternative options for the management of DMO and provided patients with choices that have higher chances of improving vision than laser alone. In Australia, since the 2008 NHMRC guidelines, there have been significant developments in both the treatment options and treatment schedules for DMO. This working group was therefore assembled to review and address the current management options available in Australia.

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.

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.

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.

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.

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.

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.

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. METHODS: A prospective series of 27 consecutive patients with CNV underwent translocation at Moorfields Eye Hospital, London between May 2003 and May 2006. RESULTS: Validation of the slit-lamp fixation task revealed 100% concordance in classification of fixation between the slit-lamp task and the microperimeter. At an average follow up of 12.2 months, the mean Early Treatment of Diabetic Retinopathy Study distance acuity improved from logMAR 0.88 to 0.68 (P < 0.03). Sixty-six per cent of patients achieved an acuity of < or =logMAR 0.8 (6/30), 22% an acuity of < or =logMAR 0.3 (6/12) and 33% gained three lines of acuity. The mean MN Read reading acuity improved from logMAR 1.23 to 0.91 (P < 0.01). Forty-four per cent of patients achieved an acuity of > or =logMAR 0.7 (N10), 15% an acuity of > or =logMAR 0.4 (N5) and 44% gained three lines of acuity. DISCUSSION: We have demonstrated a simple case selection algorithm that is based on residual foveal function and suggests good outcomes. The strongest indicators of foveal function are fixation characteristics and duration of visual loss. In contrast to previous studies, our algorithm suggests good outcomes independently of preoperative visual acuity and CNV characteristics.

YAG curios #2: Nd:YAG laser treatment following suction posterior capsulorhexis.

Suction posterior capsulorhexis (SPC) is a relatively new technique for creating a posterior capsulorhexis. We present a case series of seven patients who required Nd:YAG laser treatment 27 months after SPC. No patient had pre-existing risk factors for increased postoperative inflammation and all received a one-piece polymethylmethacrylate intraocular lens placed in-the-bag. Although it reduces the need for Nd:YAG laser treatment, SPC, like the more usual forceps posterior capsulorhexis, does not completely eliminate it.

YAG curios #1: repeat Nd:YAG laser posterior capsulotomy.

A descriptive case series of five patients identified either opportunistically or from a retrospective review of the laser register is presented. All underwent cataract surgery between 1995 and 1999 and required initial Nd:YAG laser posterior capsulotomy 15-30 months after surgery. They subsequently developed reclosure of the capsulotomy, necessitating repeat laser capsulotomy 11-82 months later. One patient, who received a hydrogel intraocular lens, required a third capsulotomy after a further 12 months. The rate of repeat Nd:YAG laser capsulotomy in our unit was 0.31%.