Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Visual outcome after removal of silicone oil in patients undergoing retinectomy for complex retinal detachment.

AIM: To evaluate the functional outcome after removal of silicone oil (ROSO) in patients undergoing retinectomy for complex retinal detachment. METHODS: We performed a retrospective case note review of patients who underwent ROSO after retinectomy for complex retinal detachment. Patients with less than 6mo follow up and recurrent retinal detachment following ROSO were excluded. RESULTS: Thirty-six patients were included. The mean best corrected visual acuity (BCVA) pre-ROSO was 1.13 logMAR (SD 0.5). The mean BCVA 3mo following ROSO was 1.16 logMAR (SD 0.53), 6mo following ROSO 1.13 (SD 0.63), and 12mo following ROSO 1.18 (SD 0.69). At 12mo after ROSO, the BCVA improved in 38.9% of patients, remained unchanged in 25%, and deteriorated in 36.1%, although there was no statistical significant difference in BCVA after ROSO at 3, 6 and 12mo (P=0.93). The size of retinectomy ranged from 15° to 270° (SD 53) and did not influence the visual outcome (P=0.11). CONCLUSION: There was no statistically significanT difference in BCVA between pre- and post- ROSO following retinectomy for complex retinal detachment. There was no statistical difference in visual outcome related to the size of the retinectomy.

Risk factors for visual impairment in patients with sickle cell disease in London.

PURPOSE: Dramatically improved health care in recent years has increased the life expectancy of patients with sickle cell disease (SCD) as well as the prognosis for its ocular complications. We sought to identify risk factors for visual impairment in patients with SCD in London 4 decades after Goldberg's seminal studies. METHODS: Patients 16 years and older with SCD (genotypes HbSS, HbSC, HbSß-thalassemia) attending hematology and ophthalmology services were offered ocular examination. Retinopathy was graded according to the Goldberg classification. Visual impairment was defined as corrected distance visual acuity of 20/40 or poorer. RESULTS: In total, 182 eyes of 182 patients (mean ± SD age, 37.2 ± 12.8 years; female, 65.9%) were included. Women were significantly older than men (mean ± SD age, 38.8 ± 13.1 vs 34.2 ± 11.8 years; p = 0.0174). There was no difference in mean age of each genotype group (p>0.15). Risk factors for sight-threatening proliferative sickle retinopathy (PSR) were age over 35 years (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.05-3.89; p = 0.0359) and HbSC genotype (OR 4.06; 95% CI 2.07-7.98; p<0.0001). Although visual impairment was related to the presence of sight-threatening PSR (OR 7.23; 95% CI 1.50-35.0; p = 0.0138), it was not related to hemoglobin genotype (p>0.50). CONCLUSIONS: We present the largest study of ocular findings in SCD in the United Kingdom. Sight-threatening PSR is a risk factor for visual impairment, but hemoglobin genotype status is not.

Spectral domain optical coherence tomography findings in long-term silicone oil-related visual loss.

PURPOSE: To investigate spectral domain optical coherence tomography findings in long-term silicone oil-related visual loss. METHODS: Four symptomatic patients were reviewed 4 years to 9 years after vitrectomy with silicone oil tamponade for macula-on retinal detachment. Three lost vision with oil in situ, with one at the time of oil removal. Eleven control eyes with good vision were included. Patients underwent assessment of best-corrected visual acuity, contrast sensitivity, Farnsworth-Munsell 100 Hue testing, static perimetry, and spectral domain optical coherence tomography imaging of the macula and disk. RESULTS: Long-term best-corrected visual acuity was significantly reduced in affected eyes (range, 0.44-1.02), as was contrast sensitivity (0.75-1.35) and color discrimination (Farnsworth-Munsell-100 Hue score, 151-390). Static perimetry showed a central scotoma in all affected eyes. Optical coherence tomography revealed microcystic macular changes in the inner nuclear layer of all affected eyes associated with severe loss of the papillofoveal retinal nerve fiber layer. In one patient, serial optical coherence tomography images showed development of microcystic macular changes 18 months after oil removal. Control eyes lacked these features, except two asymptomatic eyes that showed microcystic changes on optical coherence tomography with a corresponding paracentral scotoma. CONCLUSION: We have demonstrated microcystic macular changes in the inner nuclear layer of affected eyes, as well as focal severe loss of the papillofoveal projection. These changes share significant morphologic features reported in multiple sclerosis-associated optic neuritis and Leber hereditary optic neuropathy.

Characteristics of rhegmatogenous retinal detachments secondary to retinal dialyses.

OBJECTIVE: The pattern of retinal features in patients with retinal detachment caused by retinal dialyses is poorly described. The association with trauma has also been inconsistently reported. The authors aim to analyze patient and retinal characteristics in such cases and identify the proportion where trauma is likely causative mechanism. DESIGN: Retrospective case series. PARTICIPANTS: Sixty-three eyes from 63 patients with retinal detachment secondary to retinal dialysis. METHODS: Population was selected from consecutive patients presenting to a single surgeon at a tertiary referral vitreoretinal service (2001-2010). RESULTS: Sixty-three patients were identified (4.4% incidence rate). The cohort had a mean age of 32 years with a male preponderance (67%). Seventy-one percent had a single break, 21% had 2 breaks, and 8% had 3 to 7 breaks. Six percent of eyes had dialyses smaller than 0.5 disc diameters. Eighty-one percent of eyes had inferotemporal dialyses, but other quadrants also were involved in 25%, or exclusively in 17.5%. The primary success rate for surgery was 92% (94% final success). The presence of proliferative vitreoretinopathy (PVR) was rare (4 cases) but was a significant factor in failure of retinal reattachment (p < 0.001). Twenty-two percent were regarded as traumatic (93% male; p < 0.05). Other variables were similar between traumatic and nontraumatic eyes. CONCLUSIONS: Most retinal dialyses are located inferotemporally; however, multiple dialyses, small dialyses, and dialyses that involve multiple quadrants may be seen. In patients with evidence of direct globe injury, no difference in the pattern of retinal presentation of the dialyses was observed. Although surgical success rates are high, patients with PVR had poor response to surgery.

Characteristics of rhegmatogenous retinal detachment and their relationship to success rates of surgery.

PURPOSE: To determine features of rhegmatogenous retinal detachment predictive of anatomical success with surgical procedure. METHODS: All patients undergoing surgery at a tertiary referral practice had contemporaneous data collection in an electronic database. Overall, 847 eyes from 847 patients undergoing surgical procedure for rhegmatogenous retinal detachment were included in this study. RESULTS: Mean age was 62.2 years with 60% male subjects and 56% right eyes. Mean postoperative follow-up was 9.6 months (range, 6 weeks to 10 years). With univariate analysis, the presence of superotemporal breaks was associated with a reduction in the chance of failed primary surgery (P = 0.005); detached inferonasal breaks (P = 0.002), proliferative vitreoretinopathy (PVR) (P < 0.0001), breaks in detached inferior retina (P < 0.0001), fovea off (P = 0.001), and 4-quadrant rhegmatogenous retinal detachment (P < 0.0001) increased the risk of failure. After multivariate analysis PVR, detached inferior breaks, increased number of breaks, and 4-quadrant detachment remained associated with an increased risk of failure, and superotemporal detached breaks with the reduced risk of failure (r(2) = 0.08). For patients without PVR, only inferonasal detached breaks and 3 to 4 quadrants of detachment remained predictive of failure (r(2) = 0.04). For patients with PVR (n = 120), multivariate analysis showed that PVR C4-12 and posterior breaks increased the failure risk and detached superotemporal breaks reduced the risk of failure (r(2) = 0.22). CONCLUSION: Number of breaks, inferior positioning of breaks, the extent of rhegmatogenous retinal detachment, and PVR are associated with failed primary surgery.

The pattern and distribution of retinal breaks in eyes with rhegmatogenous retinal detachment.

PURPOSE: To identify which presenting features of rhegmatogenous retinal detachment (RRD) suggest the presence of multiple retinal breaks and to ascertain relevant patterns in retinal break location. DESIGN: Observational single-center case series. METHODS: We collected data from 851 eyes undergoing surgery for RRD between January 2001 and September 2011. Data recorded included patient demographics; extent of RRD; and the size, location, and number of retinal breaks. Statistical regression was used to identify risk factors for the presence of multiple breaks and to analyze patterns in break location. RESULTS: Of 851 patients, 7 patients were excluded because of insufficient data. Of 844 patients analyzed, 60% were male. The mean age was 62 years. Three hundred twenty-eight eyes (38.9%) had solitary breaks, whereas 58.8% had breaks in more than 1 quadrant. The superotemporal (ST) quadrant was involved most frequently (582 eyes; 69%). The superonasal and inferotemporal quadrants were involved in 341 (40%) and 274 (32%) eyes, respectively. The inferonasal (IN) quadrant was involved the least frequently (144 eyes; 17%). Of 328 eyes with only 1 break, it was most likely to be in the ST quadrant (182 eyes; 55%) and least likely to be in the IN quadrant (19 eyes; 6%). The risk of having multiple breaks was highest for patients with inferior breaks. Eyes with an IN quadrant break were almost twice as likely to harbor further breaks compared with eyes with an ST quadrant break. Vitreous hemorrhage at presentation was associated with larger breaks. ST quadrant breaks were most likely to be detached (92%), whereas IN quadrant breaks were least likely to be detached (60%). CONCLUSIONS: The ST quadrant is the most likely location for retinal breaks, the most frequently involved quadrant in eyes with solitary breaks, and has the highest proportion of detached breaks. By contrast, the IN quadrant is the least likely location for a break, the least frequently involved quadrant in eyes with solitary breaks, and the most likely location for attached breaks. The presence of an inferior (especially IN quadrant) retinal break should raise suspicion that the eye harbors further breaks.

Giant retinal tears.

A giant retinal tear (GRT) is a full-thickness neurosensory retinal break that extends circumferentially around the retina for three or more clock hours in the presence of a posteriorly detached vitreous. Its incidence in large population-based studies has been estimated as 1.5% of rhegmatogenous retinal detachments, with a significant male preponderance, and bilaterality in 12.8%. Most GRTs are idiopathic, with trauma, hereditary vitreoretinopathies and high myopia each being causative in decreasing frequency. The vast majority of GRTs are currently managed with a pars plana vitrectomy; the use of adjunctive circumferential scleral buckling is debated, but no studies have shown a clear anatomical or visual advantage with its use. Similarly, silicone oil tamponade does not influence long-term outcomes when compared with gas. Primary and final retinal reattachment rates are achieved in 88% and 95% of patients, respectively. Even when the retina remains attached, however, visual recovery may be limited. Furthermore, fellow eyes of patients with a GRT are at higher risk of developing retinal tears and retinal detachment. Prophylactic treatment under these circumstances may be considered but there is no firm evidence of its efficacy at the present time.

Morphision: a method for subjective evaluation of metamorphopsia in patients with unilateral macular pathology (i.e., full thickness macular hole and epiretinal membrane).

BACKGROUND: Lack of clinical tests to quantify spatial components of distortion in patients with full thickness macular holes (FTMH) and epiretinal membranes (ERM). AIM: To develop a test for subjective evaluation of visual distortion in the central visual field around fixation in patients with unilateral FTMH or ERM. SETTINGS AND DESIGN: Prospective case-control study carried out at tertiary referral center. MATERIALS AND METHODS: Twenty-five patients with unilateral macular disease (13 macular epiretinal membranes, 12 full-thickness macular holes), and nine controls (without ocular pathology) underwent ophthalmological examination with logMAR ETDRS visual acuity, near vision and contrast sensitivity assessed. Macular optical coherence tomography and metamorphopsia assessment using Morphision test was also carried out. This test consists of a set of modified Amsler charts for detection, identification, and subjective quantification of visual distortion in the central visual field around fixation. Morphision test content and construct validity, and reliability (test-retest method) were evaluated. Sixteen patients completed an unstructured survey on test performance and preference. RESULTS: Every patient with unilateral FTMH or ERM identified a particular chart using Morphision test (content validity). None of the normal subjects without symptoms of metamorphopsia identified any distortion (construct validity). Test-retest showed a 100% consistency for frequency and 67% for amplitude. The mean amplitude difference between measurements was 0.02 degrees (SD = 0.038). The coefficient of repeatability was 0.075. There was a correlation between Morphision amplitude score and visual acuity and contrast sensitivity, individually. CONCLUSIONS: Morphision test allowed detection and subjective quantification of metamorphopsia in the clinical setting in our patients with unilateral macular epiretinal membranes and full thickness macular holes.

Macular displacement following rhegmatogenous retinal detachment repair.

AIMS: To investigate the incidence of macula displacement and symptoms of distortion following rhegmatogenous retinal detachment (RRD) repair, quantify the displacement where seen and further characterise the nature of the displacement. METHODS: Consecutive patients undergoing primary RRD repair were assessed postoperatively with fundus autofluorescence and optical coherence tomography imaging, and the extent of macula displacement quantified using a novel means. Findings were examined for correlations with symptoms and pre-operative features. RESULTS: Macula displacement was evident postoperatively in 72% of 32 consecutive fovea-involving detachments treated with vitrectomy and gas. It was also evident in 5/17 foveal-sparing cases treated with vitrectomy and gas and in two of two patients with fovea-involving detachments treated with vitrectomy and oil. There was a significant correlation between the presence of macula displacement and symptoms of distortion in the early postoperative period (p=0.013). Symptomatic patients described bending of lines with or without objects appearing smaller or narrower in the operated eye. Quantifying the displacement demonstrated that the extent of displacement was associated with distance from the optic disc (p=0.005) and the extent of retinal detachment. CONCLUSIONS: Displacement of the macula is common following RRD repair and heterogeneous in nature. Most affected patients are symptomatic in the early postoperative period.

Consecutive toxic anterior segment syndrome in combined phaco-vitrectomy.

Toxic anterior segment syndrome (TASS), though rare, has been well documented following anterior segment surgery but not following vitrectomy (Monson et al., J Cataract Refract Surg 18:184-189, 1992). It typically presents within 24 h of uncomplicated cataract surgery with minimal or no pain and intense anterior segment inflammation (Monson et al. 1992). Various exogenous chemicals have been identified as the cause of TASS (Kutty et al., Cataract Refract Surg, 34:585-590 2008; Liu et al., J Cataract Refract Surg 27:1746-1750, 2001).

Spectral domain optical coherence tomography demonstrates interconnected orbital cyst and chorioretinal coloboma in an adult.

PURPOSE: To report an orbital cyst underlying a chorioretinal coloboma in an otherwise normal eye, detected by spectral domain optical coherence tomography imaging. To the authors' knowledge, this is the first case of a chorioretinal colobomatous cyst in the normal eye to be reported. METHODS: A descriptive case report of a patient with a chorioretinal coloboma with an underlying orbital cyst. RESULTS: A 59-year-old woman presented with a floater affecting her left visual field. Fundoscopy revealed a pale lesion inferotemporal to fixation at the left macula. Spectral domain optical coherence tomography revealed a retinochoroidal coloboma with an associated scleral hole. Enhanced depth imaging spectral domain optical coherence tomography revealed an underlying orbital colobomatous cyst. CONCLUSION: To the authors' knowledge, this is the first case of a healthy adult with a retinochoroidal colobomatous cyst without microphthalmos. The authors encourage optical coherence tomography of any suspected colobomas to exclude similar pathology.

Air-gas exchange reevaluated: clinically important results of a computer simulation.

PURPOSE: The primary aim of this study was to evaluate the efficiency of air-gas exchange techniques and the factors that influence the final concentration of an intraocular gas tamponade. Parameters were varied to find the optimum method of performing an air-gas exchange in ideal circumstances. METHODS: A computer model of the eye was designed using 3D software with fluid flow analysis capabilities. Factors such as angular distance between ports, gas infusion gauge, exhaust vent gauge and depth were varied in the model. Flow rate and axial length were also modulated to simulate faster injections and more myopic eyes, respectively. The flush volume of gas required to achieve a 97% intraocular gas fraction concentration were compared. RESULTS: Modulating individual factors did not reveal any clinically significant difference in the angular distance between ports, exhaust vent size, and depth or rate of gas injection. In combination, however, there was a 28% increase in air-gas exchange efficiency comparing the most efficient with the least efficient studied parameters in this model. The gas flush volume required to achieve a 97% gas fill also increased proportionately at a ratio of 5.5 to 6.2 times the volume of the eye. CONCLUSIONS: A 35-mL flush is adequate for eyes up to 25 mm in axial length; however, eyes longer than this would require a much greater flush volume, and surgeons should consider using two separate 50-mL gas syringes to ensure optimal gas concentration for eyes greater than 25 mm in axial length.

Primary Wegener's granulomatosis of the orbital apex with initial optic nerve infiltration.

Wegener's granulomatosis can involve the orbit and sometimes the optic nerve. This usually occurs as a result of contiguous spread from affected sinuses or extraocular muscles, or from a vasculitic posterior optic neuropathy. However, we present an unusual case of isolated orbital apex infiltrative disease in a patient with known Wegener's granulomatosis. This initially caused painless optic neuropathy and progressed to painful ophthalmoplegia and blindness. Optic nerve biopsy, performed to exclude methotrexate-induced lymphoma, confirmed optic nerve infiltration. The condition was refractory to high-dose pulsed methylprednisolone but the patient gained symptomatic relief from rituximab. Wegener's granulomatosis should be considered in cases of isolated posterior optic neuropathy, and close attention should be placed on imaging the orbital apex.

Effect of cataract extraction on the glaucoma progression index (GPI) in glaucoma patients.

PURPOSE: To determine the effect of cataract extraction on the glaucoma progression index (GPI) in glaucoma patients with coexisting cataract. PATIENTS AND METHODS: This is a retrospective noncomparative study. Consecutive eligible patients with glaucoma who underwent phacoemulsification alone or in combination with augmented trabeculectomy were included. All patients had Swedish Interactive Threshold Algorithm-standard 24-2 visual fields within 10 months of surgery. Exclusion criteria included other ocular morbidity, intraoperative complications, and perimetric reliability indices greater than 33%. Comparison was made between the immediate visual fields before and after surgery. The main outcome measure was the change in GPI. Changes in the pattern standard deviation (PSD) and mean deviation (MD) were also assessed. Comparison of means was performed with the paired t test. RESULTS: Thirty-three eyes of 33 patients (all Whites) were analyzed. The mean age at surgery was 77.0+/-8.7 years. Visual field tests were performed 3.3+/-3.0 months SD before surgery and 5.4+/-2.6 months after surgery. There was a statistically significant increase in the GPI after cataract surgery (from 71.5+/-18.5% to 74.6+/-17.1%; P=0.02). The improvement in MD was also statistically significant (from -11.8+/-5.3 to -10.2+/-5.3 dB; P <0.01), but the change in PSD did not reach statistical significance. CONCLUSIONS: Uncomplicated cataract extraction resulted in a statistically significant improvement in the 24-2 Swedish Interactive Threshold Algorithm-standard GPI and MD, but not in PSD. Both the MD and the GPI may be influenced by lens opacities, which could make detection of glaucoma visual field progression more difficult for clinicians in glaucoma patients with concurrent cataract.

The quality of reporting of diagnostic accuracy studies in glaucoma using scanning laser polarimetry.

PURPOSE: Scanning laser polarimetry (SLP) has been proposed as a useful diagnostic test for glaucoma. This study was conducted to evaluate the quality of reporting of published studies using the SLP for diagnosing glaucoma. METHODS: A validated Medline and hand search of English-language articles reporting on measures of diagnostic accuracy of the SLP for glaucoma was performed. Two reviewers independently selected and appraised the manuscripts. The Standards for Reporting of Diagnostic Accuracy (STARD) checklist was used to evaluate the quality of each publication. RESULTS: A total of 47 papers were identified of which the first 10 (from 1997 to 2000) and the last 10 articles (from 2004 to 2005) were appraised. Interobserver rating agreement of STARD items was high (85.5% agreement, kappa=0.796). The number of STARD items properly reported ranged from 3/25 to 19/25. Only a quarter of studies (5/20) explicitly reported more than half of the STARD items. Important aspects of the methodology were often missing such as participant sampling (reported in 40% of manuscripts), masking of the readers of the index test and reference standard (reported in 20% of manuscripts), and estimation of uncertainty (eg, 95% confidence intervals, reported in 25% of manuscripts). There was a slight increase in the number of STARD items reported with time. CONCLUSIONS: The quality of reporting of diagnostic accuracy tests for glaucoma with SLP is suboptimal. The STARD initiative may be a useful tool for appraising the strengths and weaknesses of diagnostic accuracy studies.

The quality of reporting of diagnostic accuracy studies in glaucoma using the Heidelberg retina tomograph.

PURPOSE: Scanning laser tomography with the Heidelberg retina tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany) has been proposed as a useful diagnostic test for glaucoma. This study was conducted to evaluate the quality of reporting of published studies using the HRT for diagnosing glaucoma. METHODS: A validated Medline and hand search of English-language articles reporting on measures of diagnostic accuracy of the HRT for glaucoma was performed. Two reviewers selected and appraised the papers independently. The Standards for Reporting of Diagnostic Accuracy (STARD) checklist was used to evaluate the quality of each publication. RESULTS: A total of 29 articles were included. Interobserver rating agreement was observed in 83% of items (kappa=0.76). The number of STARD items properly reported ranged from 5 to 18. Less than a third of studies (7/29) explicitly reported more than half of the STARD items. Descriptions of key aspects of the methodology were frequently missing. For example, the design of the study (prospective or retrospective) was reported in 6 of 29 studies, and details of participant sampling (e.g., consecutive or random selection) were described in 5 of 29 publications. The commonest description of diagnostic accuracy was sensitivity and specificity (25/29) followed by area under the ROC curve (13/29), with 9 of 29 publications reporting both. CONCLUSIONS: The quality of reporting of diagnostic accuracy tests for glaucoma with HRT is suboptimal. The STARD initiative may be a useful tool for appraising the strengths and weaknesses of diagnostic accuracy studies.