Treatment outcomes for maculopathy secondary to retinal vein occlusion in Afghanistan.

OBJECTIVES: The objective of this study was to investigate the efficacy of intravitreal antivascular endothelial growth factor (VEGF) therapy in the treatment of macular edema secondary to retinal vein occlusion (RVO) in Afghanistan. METHODS: A retrospective analysis was conducted of all RVO cases that underwent intravitreal ant-VEGF injection at the two leading hospitals in Kabul. The main outcome measures were visual acuity and central retinal thickness as determined by optical coherence tomography. Information was also collected on the distance traveled by each patient and the frequency of injections. RESULTS: One hundred and twenty-five eyes of 121 patients (86 males) with RVO were identified as having undergone treatment, with a mean age of 53.1 years (range 20-80). The only agent used was bevacizumab. The mean central retinal thickness reduced from 624.2 ± 24.9 µm at the baseline to 257.8 ± 5.7 µm following treatment (P < 0.001). There was a small increase in visual acuity from 1.33 LogMAR at the baseline to 1.13 LogMAR following the most recent injection (P = 0.03, paired t-test). The mean distance traveled by patients was 173.9 km (range 2-447 km). CONCLUSION: Despite the challenges of health-care provision in Afghanistan, this review shows that the use of intravitreal bevacizumab has provided an effective treatment for macular edema after RVO.

PHOTORECEPTOR DAMAGE IN TERSON SYNDROME.

PURPOSE: To describe photoreceptor damage in patients with Terson syndrome as a potential cause for inconsistent clinical outcomes. METHODS: Clinical evaluation and retinal imaging in six patients. RESULTS: Four patients were women and two men, with an average age of 46.8 years (SD 8.9). Four patients suffered aneurysmal subarachnoid hemorrhage, one vertebral artery dissection, and one superior sagittal sinus thrombosis. In 11 eyes, a consistent pattern of outer retinal changes within the central retina affecting the ellipsoid zone and the outer nuclear layer was observed, indicating photoreceptor damage. Areas of photoreceptor damage showed poor spatial correlation with intraocular hemorrhage, particularly subinternal limiting membrane hemorrhage. The observed retinal abnormalities demonstrated incomplete recovery over long-term follow-up 3.5 to 8 years posthemorrhage, irrespective of surgical or conservative treatment strategy, and had variable impact on the patients' visual function. CONCLUSION: The observations suggest that photoreceptor damage in Terson syndrome likely represents a distinct manifestation of this condition, which could be caused by transient ischemia of the outer retina secondary to acute rise in intracranial pressure.

Surgical outcomes in only eye cataract surgery.

INTRODUCTION: Performing cataract surgery in the setting of only one seeing-eye has significant benefits but also potential negative consequences for both patient and surgeon. This study investigates the surgical outcomes in patients undergoing cataract surgery on their only seeing-eye. METHODS: A retrospective analysis was conducted in a single tertiary centre of all adult patients who had undergone cataract surgery on their only eye, where the fellow eye had a vision of 1.0 LogMAR or worse. Complication rates and visual outcomes were compared against data from the National Ophthalmology Database (NOD) Audit. RESULTS: 918 patients underwent cataract surgery on their only seeing-eye and had their postoperative visual acuity recorded. The overall unadjusted complication rate was 4.0% (versus 2.5% from NOD data) with the rate of posterior capsule rupture (PCR) being 1.9% (versus 1.14% from NOD data). 72.5% (versus 91.5% from NOD data) of patients attained a post-operative visual acuity of 0.3 LogMAR or better. The grade of surgeon performing the surgery did not have a statistically significant effect on the risk of complications. DISCUSSION: In this cohort of only-eye patients undergoing cataract surgery, there was a small increased risk of operative complications including an increased, unadjusted risk of PCR, and fewer eyes achieved 0.3 LogMAR vision post-operatively compared to the NOD audit data. Grade of surgeon did not have an impact on the complication rate, indicating that with appropriate supervision, trainee surgeons may gain experience in only-eye surgery without additional risk to the patient. Further multicentre studies are recommended to assess reproducibility across units.

The Effect of Cataract on Color Vision Measurement with the Low-Vision Cambridge Colour Test: Providing an Adjustment Factor for Clinical Trials.

Purpose: To quantify the effect of cataract on color vision as measured by the low-vision Cambridge Colour Test (lvCCT; Cambridge Research Systems) and to understand whether different types and severities of cataract have different effects on color vision. Design: Cohort study. Participants: Patients aged 18 to 95 undergoing routine cataract surgery at the Oxford Eye Hospital. Methods: The lvCCT was performed to measure color sensitivity in both eyes both before and after surgery. The crystalline lens was examined and graded according to the Lens Opacities Classification System III to determine the type and severity of cataract. Measures of repeatability were performed for the data to explore test-retest bias using Bland-Altman analysis. The Wilcoxon signed-rank test was performed to assess the effect of cataract on color vision by comparing control and surgical test measurements. Three multiple linear regressions were performed to relate cataract grading or severity to color vision measurements. Main Outcome Measures: Color discrimination along each of the protan, deutan, and tritan confusion lines. Results: The Wilcoxon signed-rank test showed a statistically significant difference in both the protan (P = 0.024) and tritan (P = 0.020) axes on comparison of control and surgical test measurements. As severity of cataract increased, color vision sensitivity was affected more greatly, and nuclear sclerotic cataract showed the most profound effect on color vision sensitivity in the lvCCT; however, the linear regression models showed that these observations did not reach statistical significance. Conclusions: Cataract surgery has a statistically significant effect on color vision in both the protan and tritan axes. The effects of specific subtypes of cataract and different severities could not be elucidated because of the high prevalence of patients with mixed cataract. The lvCCT color sensitivity measurements are used regularly as outcome measures in clinical gene therapy trials involving vitreoretinal surgery, and vitrectomy accelerates cataract formation. Therefore, it is important to quantify the effect of cataract on color vision measurements so that it may be taken into account when used as an outcome measure in clinical trials. We were unable to derive a precise correction factor for cataract on color vision measurements.

Analysis of Early Cone Dysfunction in an In Vivo Model of Rod-Cone Dystrophy.

Retinitis pigmentosa (RP) is a generic term for a group of genetic diseases characterized by loss of rod and cone photoreceptor cells. Although the genetic causes of RP frequently only affect the rod photoreceptor cells, cone photoreceptors become stressed in the absence of rods and undergo a secondary degeneration. Changes in the gene expression profile of cone photoreceptor cells are likely to occur prior to observable physiological changes. To this end, we sought to achieve greater understanding of the changes in cone photoreceptor cells early in the degeneration process of the Rho-/- mouse model. To account for gene expression changes attributed to loss of cone photoreceptor cells, we normalized PCR in the remaining number of cones to a cone cell reporter (OPN1-GFP). Gene expression profiles of key components involved in the cone phototransduction cascade were correlated with tests of retinal cone function prior to cell loss. A significant downregulation of the photoreceptor transcription factor Crx was observed, which preceded a significant downregulation in cone opsin transcripts that coincided with declining cone function. Our data add to the growing understanding of molecular changes that occur prior to cone dysfunction in a model of rod-cone dystrophy. It is of interest that gene supplementation of CRX by adeno-associated viral vector delivery prior to cone cell loss did not prevent cone photoreceptor degeneration in this mouse model.

A Novel Achromatopsia Mouse Model Resulting From a Naturally Occurring Missense Change in Cngb3.

Purpose: A local colony of inbred mice (129S6/SvEvTac origin), in isolation for over a decade, were found to have absent light-adapted electroretinogram (ERG) responses. We investigated the inheritance and genetic basis of this phenotype of cone photoreceptor function loss. Methods: An affected 129S6/SvEvTac colony animal was outcrossed to a C57BL/6J mouse and intercrossed to investigate inheritance in the F2 generation. We performed ERG testing and targeted resequencing on genes of interest (Gnat2, Cnga3, Cngb3, Pde6c, Hcn1, Syne2). The eyes of a subset of animals underwent histologic immunostaining. Results: All 129S6/SvEvTac colony animals tested lacked cone pathway function by ERG testing (n = 12), although rod pathway-based ERG responses remained unaffected. Outcross-intercross breeding showed a recessive inheritance pattern. A novel missense mutation was identified in the Cngb3 gene, which causes an amino acid substitution at a conserved residue (NM_013927)c.692G>A; p.(R231H). The recessive phenotype only affected homozygotes (χ2 = 39, P = 3.2e-10). Cones had normal morphology at postnatal day (PND) 70, but cone cell counts declined from PND 30 to PND 335 (P = 0.038), indicating progressive cone photoreceptor death. Conclusions: We identified the spontaneous occurrence of a 10th model of cone photoreceptor function loss (cpfl10) in an isolated line of inbred mice. Our results indicate that this is caused by a novel missense mutation in the Cngb3 gene, with a fully recessive inheritance pattern. This mouse may provide a more appropriate background against which to assess CNGB3 achromatopsia gene therapy for missense mutations.

A quality of life survey in patients with long-term silicone oil or phthisis bulbi.

AIM: The aim of this study is to determine whether there is any difference in the quality of life of patients with a blind eye with long-term silicone oil compared to without. METHOD: Patients with either long-term silicone oil in situ (N = 17), defined as a period greater than 6 months duration with no plan for future removal, or those with a phthisical, non oil-filled eye were identified (N = 13). Two validated questionnaires (NEI VFQ-25 and the FACE-Q) that cover indicators for visual function, pain and cosmesis were sent to all patients in the two cohorts. RESULTS: There was no significant difference found in quality of life outcomes between the two groups in terms of visual function, pain or cosmesis. CONCLUSION: The results of this study support a holistic approach to the consent process before vitreoretinal surgery. Patients that may need to undergo multiple vitreoretinal procedures, where the endstage result is a long-term silicone oil fill, should be informed that their functional outcome may be similar to having no surgical intervention.

IgG4-related disease presenting as posterior scleritis and vitritis, progressing to multifocal orbital involvement.

IgG4-related disease (IgG4-RD) is a rare, chronic inflammatory condition that may involve nearly every organ system. Originally identified as a cause of autoimmune pancreatitis, its characteristic histological and clinical features have been found in a wide variety of inflammatory presentations, including the eye and orbit. Here we describe an example of a case of IgG4-RD initially presenting as scleritis and vitritis, with further progression to multifocal bilateral orbital involvement. Tissue biopsy of an orbital mass was highly characteristic of IgG4-RD histology and a rapid clinical response to corticosteroids was observed. This case highlights IgG4-RD as a rare cause of intraocular inflammation that may progress to involve the orbit.

Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion.

Photoreceptor transplantation is a potential future treatment for blindness caused by retinal degeneration. Photoreceptor transplantation restores visual responses in end-stage retinal degeneration, but has also been assessed in non-degenerate retinas. In the latter scenario, subretinal transplantation places donor cells beneath an intact host outer nuclear layer (ONL) containing host photoreceptors. Here we show that host cells are labelled with the donor marker through cytoplasmic transfer-94±4.1% of apparently well-integrated donor cells containing both donor and host markers. We detect the occurrence of Cre-Lox recombination between donor and host photoreceptors, and we confirm the findings through FISH analysis of X and Y chromosomes in sex-discordant transplants. We do not find evidence of nuclear fusion of donor and host cells. The artefactual appearance of integrated donor cells in host retinas following transplantation is most commonly due to material transfer from donor cells. Understanding this novel mechanism may provide alternate therapeutic strategies at earlier stages of retinal degeneration.

Unsutured phakic implantation of a black intraocular lens in the sulcus to treat leukocoria.

UNLABELLED: We describe a 40-year-old woman with von Hippel-Lindau syndrome, secondary chronic exudative retinal detachment, and white cataract with consequent leukocoria. Because the cataract was contracted and calcified, a black Morcher 85F poly(methyl methacrylate) IOL was implanted in the ciliary sulcus anterior to the lens to prevent posterior capsule rupture and potential destabilization of the retinal detachment with a risk for phthisis. Excellent centration of the black IOL was achieved with good cosmetic outcome and without postoperative uveitis or glaucoma. We suggest that this is a rare indication for implantation of an IOL designed for the sulcus but in the presence of the crystalline lens. This approach makes IOL removal, if necessary at a later date, relatively straightforward. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Cone photoreceptor neuroprotection conferred by CNTF in a novel in vivo model of battlefield retinal laser injury.

PURPOSE: To develop a reproducible laboratory model to simulate a battlefield foveal laser injury and to test potential neuroprotective effects of a single injection treatment that might be administered in a military setting. METHODS: Frequency-doubled 532-nm Nd:YAG laser was used to induce a threshold retinal injury bilaterally in transgenic reporter mice that have fluorescent cones. Intravitreal injection of ciliary neurotrophic factor (CNTF) was then administered to the lasered eye and compared with a contralateral sham injection of saline. The effect on fluorescent cone cell survival was quantified using a confocal scanning laser ophthalmoscope (cSLO), TUNEL assays, and quantitative real-time PCR (qPCR). RESULTS: At 3 weeks post-laser, cSLO imaging showed that the proportion of surviving cones expressing green fluorescent protein (GFP) was greater in CNTF-treated (54.1 ± 5.15% of baseline count) than in sham-injected eyes (28.7 ± 4.4%), which was accompanied by a reduction in TUNEL-positive cells. This difference in cone survival persisted at the 6-week point (treated, 39.6 ± 3.2% versus sham, 18.0 ± 3.8%). These changes were accompanied by a reduction in TUNEL-positive cells. The Bcl-2/Bax ratio was increased in CNTF-treated eyes at 1 week postlaser exposure relative to controls. CONCLUSIONS: A single intravitreal injection of CNTF protein was shown to improve cone survival when administered immediately after laser exposure. Similar treatments with CNTF might also have a role in attenuating retinal laser damage sustained by combat personnel in the military setting.

Treatment of a lacrimal pneumocele with punctal plug insertion.

A 37-year-old man presented with symptoms of air and mucus reflux from the right medial canthus on blowing his nose. Examination showed crepitus in the region overlying the right lacrimal sac, and he was able to produce bubbles in his conjunctival lake on instillation of topical 2% fluorescein. Dacryoscintigraphy showed symmetrical slow passage of tracer from the lacrimal sac in the nasolacrimal duct indicating delay at the postsac level. Dacryocystography showed that the right lacrimal system contained round filling defects, suggesting the presence of soft tissue tumors. However, a CT scan showed an enlarged right lacrimal fossa with air in the nasolacrimal duct and no evidence of a mass. Following lower punctal plug occlusive canaliculoplasty on the right, using a preloaded silicone plug, the patient noted an immediate resolution of reflux symptoms.

Scleral contact lens usage in patients with complex blepharoptosis.

PURPOSE: To evaluate the efficacy of scleral contact lenses (ScCLs) as an alternative or as an adjunct to surgical correction for the management of complex ptosis. METHODS: A retrospective case-note review was used to determine the subjective function and cosmetic acceptability of the lenses. Digital photographs were taken, both with and without the lens in place; analytic software was used to assess the vertical height of the palpebral aperture (PA) and the upper margin-reflex distance. Three masked observers independently graded the photographs for cosmesis as "good," "moderate," or "poor." RESULTS: Ten patients (6 male) had been wearing ScCLs in 14 treated eyes for between 1 and 40 years (mean, 10.3 years; median, 3 years). Without a lens, the mean PA was 4.9 mm (median, 5.1 mm; range, 1.7-7.1 mm), increasing to 9.5 mm (median, 8.9 mm; range, 5.8-14.8 mm) with the lens in place (p < 0.005). Likewise, the upper margin-reflex distance increased from 0.39 mm (median, 0.03 mm; range, 0-2.4 mm) without a lens in place to 3.1 mm (median, 2.7 mm; range, 1.5-5.8 mm) with lens wear (p < 0.005). In 6 patients with unilateral ScCL wear, mean PA was 10.4 mm in the treated eye and 8.4 mm in the eye without a lens (p = 0.22). All patients who were wearing ScCLs long term found them to be both comfortable and cosmetically acceptable. On subjective grading of photographs, however, the cosmesis was judged as "good" in 22%, "moderate" in 64%, and "poor" in 14%. CONCLUSION: In some patients, ScCLs provide a well-tolerated and practical long-term solution to safely elevating the upper eyelid in which complex ptosis is present. The patients in our cohort seem to be satisfied with the cosmesis, although there are some limitations to this aspect when viewed subjectively.

Risk of iatrogenic peripheral retinal breaks in 20-G pars plana vitrectomy.

PURPOSE: To estimate the frequency and risk factors for entry site and other peripheral iatrogenic retinal breaks in eyes undergoing standard 20-G 3-port pars plana vitrectomy. DESIGN: Single-center, retrospective, interventional case series. PARTICIPANTS: A total of 645 eyes undergoing pars plana vitrectomy at Moorfields Eye Hospital during the period June 1, 2005, to June 1, 2006, for indications excluding rhegmatogenous retinal detachment. METHODS: Case note review. Exclusion criteria were preexisting retinal breaks or rhegmatogenous retinal detachment, previously vitrectomized eyes, and iatrogenic breaks posterior to the equator. MAIN OUTCOME MEASURES: Frequency, anatomic location, and risk factors associated with iatrogenic peripheral retinal breaks and rate of postoperative rhegmatogenous retinal detachment. RESULTS: Iatrogenic peripheral retinal breaks occurred in 98 of 645 eyes (15.2%) intraoperatively. Eleven of 645 cases (1.7%) experienced postoperative rhegmatogenous retinal detachment caused by undetected or new peripheral retinal breaks. Breaks were most common during surgery for tractional retinal detachment (22.2%), macular hole (18.1%), dislocated intraocular lens implants (16.7%), and epiretinal membrane (13.9%). Overall, breaks were more common in the superior retina (P<0.01), with 41.5% occurring in the 10 and 2 o'clock positions. Eyes requiring surgical induction of a posterior vitreous detachment had 2.9 times greater odds of developing iatrogenic peripheral retinal breaks (95% confidence interval, 1.8-4.7, P<0.001) than eyes with preexisting posterior vitreous detachment. Similarly, phakic eyes had 2.4 times higher odds (95% confidence interval, 1.42-3.96, P = 0.001) of break formation. CONCLUSIONS: Iatrogenic peripheral retinal breaks caused by vitrectomy are more common than previously indicated. Approximately 4 in 10 breaks are related to traction at sclerotomy entry sites. Eyes undergoing surgery for tractional retinal detachment seemed to have the highest risk for break formation. Similarly, phakic eyes and eyes that require induction of a posterior vitreous detachment have more than double the risk for break formation.