Exome sequencing in patients with microphthalmia, anophthalmia, and coloboma (MAC) from a consanguineous population.

Next-generation sequencing strategies have resulted in mutation detection rates of 21% to 61% in small cohorts of patients with microphthalmia, anophthalmia and coloboma (MAC), but despite progress in identifying novel causative genes, many patients remain without a genetic diagnosis. We studied a cohort of 19 patients with MAC who were ascertained from a population with high rates of consanguinity. Using single nucleotide polymorphism (SNP) arrays and whole exome sequencing (WES), we identified one pathogenic variant in TENM3 in a patient with cataracts in addition to MAC. We also detected novel variants of unknown significance in genes that have previously been associated with MAC, including KIF26B, MICU1 and CDON, and identified variants in candidate genes for MAC from the Wnt signaling pathway, comprising LRP6, WNT2B and IQGAP1, but our findings do not prove causality. Plausible variants were not found for many of the cases, indicating that our current understanding of the pathogenesis of MAC, a highly heterogeneous group of ocular defects, remains incomplete.

PIGMENTED PARAVENOUS CHORIORETINAL ATROPHY: Detailed Clinical Study of a Large Cohort.

PURPOSE: To review and describe in detail the demographics, functional and anatomical characteristics, and clinical course of pigmented paravenous chorioretinal atrophy in a large cohort of adults and children. METHODS: This is a retrospective case series of consecutive patients diagnosed with pigmented paravenous chorioretinal atrophy at a single U.K. referral center from 1974 to 2016. Clinical records, retinal imaging (color fundus photography, fundus autofluorescence, and optical coherence tomography), and electrophysiological assessments were reviewed. RESULTS: Twenty-three patients were identified (13 males and 10 females). The mean age at presentation was 35 years (range 10-67 years). Mean follow-up was 6.7 years (range 0-30 years). There was no family history of similar retinal disease. Thirteen (57%) patients were asymptomatic. Symptoms included photopsia (n = 1.4%), blurred vision (n = 4.17%), peripheral visual field loss (n = 3.13%), and nyctalopia (n = 2.8%). One patient had previous intermediate uveitis. Twenty-one (91%) patients had ≥6/12 in the better seeing eye at final follow-up; visual acuity loss over time was recorded in 2 patients. Color vision was normal in all 14 patients assessed. Paravenous hypoautofluorescence with surrounding increased fundus autofluorescence was characteristically observed. Optical coherence tomography over the retinal changes demonstrated choroidal, retinal pigment epithelium, and outer retinal layer thinning. Peripapillary atrophic changes on fundus photography were evident in 20 (87%) patients. Interocular asymmetry of fundus and electroretinography findings was common. The electroretinography findings showed a similar degree of generalized rod and cone photoreceptor dysfunction in most cases. CONCLUSION: Overall, most patients with pigmented paravenous chorioretinal atrophy maintained stable vision. The lack of other affected family members, slow or absent progression, and interocular asymmetry of the retinal features is suggestive of an acquired rather than inherited retinal disorder, which is generally nonprogressive. We identify that patients commonly have marked interocular asymmetry both on structural and functional assessment.

THE FUNDUS PHENOTYPE ASSOCIATED WITH THE p.Ala243Val BEST1 MUTATION.

PURPOSE: To describe a highly recognizable and reproducible retinal phenotype associated with a specific BEST1 mutation-p.Ala243Val. METHODS: Retrospective review of consecutive cases where genetic testing has identified p.Ala243Val BEST1 as the cause of disease. Electronic patient records were used to extract demographic, as well as functional and anatomical data. These data were compared with those observed with the most common BEST1 genotype, p.Arg218Cys. RESULTS: Eight individuals (six families) were identified with the p.Ala243Val BEST1 mutation and seven patients with the pathologic variant p.Arg218Cys. No patients with mutation of codon 243 knowingly had a family history of retinal disease, whereas all patients with the p.Arg218Cys variant did. The maculopathy was bilateral in all cases. The p.Ala243Val mutation was associated with a pattern dystrophy-type appearance, most visible with near-infrared reflectance and fundus autofluorescence imaging. This phenotype was never observed with any other genotype. This mutation was associated with an older median age of symptom onset (median = 42, interquartile range = 22) compared with those harboring the p.Arg218Cys mutation (median = 18, interquartile range = 12; Mann-Whitney U test; P < 0.05). Despite their older age, the final recorded acuity seemed to be better in the p.Ala243Val group (median = 0.55, interquartile range = 0.6475; median = 0.33, interquartile range = 0.358), although this did not reach statistical significance (Mann-Whitney U test; P > 0.05). CONCLUSION: The mutation p.Ala243Val is associated with highly recognizable and reproducible pattern dystrophy-like phenotype. Patients develop symptoms at a later age and tend to have better preservation of electrooculogram amplitudes.

DETAILED RETINAL IMAGING IN CARRIERS OF OCULAR ALBINISM.

BACKGROUND: Albinism refers to a group of disorders primarily characterized by hypopigmentation. Affected individuals usually manifest both ocular and cutaneous features of the disease, but occasionally hair and skin pigmentation may appear normal. This is the case in ocular albinism, an X chromosome linked disorder resulting from mutation of GPR143. Female carriers may be recognized by a "mud-splatter" appearance in the peripheral retina. The macula is thought to be normal, however. METHODS: Obligate female carriers of pathogenic GPR143 alleles were recruited. Molecular confirmation of disease was performed only for atypical cases. Detailed retinal imaging was performed (colour fundus photography, optical coherence tomography, fundus autofluorescence. RESULTS: Eight individuals were ascertained. A novel GPR143 mutation was identified in one family (p.Gln328Ter). Foveal fundus autofluorescence was subjectively reduced in 6/6 patients imaged. A "tapetal-like" pattern of autofluorescence was visible at the macula in 3/6. Persistence of the inner retinal layers at the fovea was observed in 6/8 females. CONCLUSION: Female carriers of ocular albinism may manifest signs of retinal pigment epithelium mosaicism at the macula and the peripheral fundus. A tapetal-like reflex on fundus autofluorescence may be considered the macular correlate of "mud-splatter."

Safety profile and efficacy of tacrolimus in the treatment of birdshot retinochoroiditis: a retrospective case series review.

AIM: Evaluation of the use of tacrolimus in the treatment of birdshot retinochoroiditis (BRC) at a tertiary referral centre with the aim to describe its safety and efficacy. METHODS: The medical records of 25 patients diagnosed with BRC at uveitis service, Moorfields Eye Hospital, and who had received tacrolimus treatment were retrospectively reviewed. The main outcome measures of the study were (1) safety of tacrolimus in terms of side effects and (2) efficacy, as measured both by control of inflammation and visual function assessed by Humphrey visual fields and electrophysiological testing over at least 6 months and then 1 year. RESULTS: Tacrolimus was commenced in 25 patients (mean age 50.4±10.8 years) and was well tolerated in 21 patients (84%). It was necessary to stop the tacrolimus in four patients. No patient showed major changes in renal function: 3/21 patients (14.28%) showed slightly abnormal (less than 30%) function at the end of the first month of treatment; 1/21 (4.76%) patients at 3 months, but at the end of a 6-month treatment period only 1/21 patients (4.76%) showed minor abnormality in renal function. The mean daily prednisolone dose was 19.7 mg at the beginning of the study, which had fallen to 6.9 mg at the end (t=5.071, p=0.001). Visual acuity mostly remained stable. Visual fields improved over time (mean improvement in Humphrey mean deviation, right eye=1.8±2.4 dB, t=3.821, p=0.004; left eye=1.9±2.7, dB, t=3.06, p=0.007). Electrophysiological function showed improvement in 10 patients, and in four patients an initial deterioration in function improved following tacrolimus dose adjustment. CONCLUSION: Tacrolimus has a good safety profile for long-term use in patients with BRC as a second-line agent enabling steroid sparing and visual function stabilisation or improvement.

NORMAL ELECTROOCULOGRAPHY IN BEST DISEASE AND AUTOSOMAL RECESSIVE BESTROPHINOPATHY.

PURPOSE: To evaluate the electrooculogram (EOG) in a large series of patients with Best disease and autosomal recessive bestrophinopathy. METHODS: A retrospective review of consecutive cases at Moorfields Eye Hospital, London, United Kingdom. Patients with Best disease or autosomal recessive bestrophinopathy who, after electrophysiologic testing, had a normal or atypical EOG light rise were identified. Main outcome measure was EOG amplitude, clinical phenotype and genotype. RESULTS: One hundred thirteen patients were identified with likely disease-causing sequence variants in BEST1 (99 Best disease and 14 autosomal recessive bestrophinopathy). Electrooculograms had been performed in 75 patients. Twenty patients (27%) had no detectable light rise (Arden ratio of 100%) and 49 (65%) had Arden ratios of between 100% to 165%. Six patients (8%) were found to have an EOG light rise of >165%. No cases demonstrated significant interocular asymmetry in EOG amplitude. CONCLUSION: The current work provides significant clinical evidence that the EOG phenotype in Best disease and autosomal recessive bestrophinopathy is more variable than currently appreciated. As a normal EOG may occur in the presence of a classical fundus appearance, the consequences of BEST1 mutation may be independently expressed, possibly mediated through differential effects on intracellular calcium homeostasis.

FUNCTIONAL AND ANATOMICAL OUTCOMES OF CHOROIDAL NEOVASCULARIZATION COMPLICATING BEST1-RELATED RETINOPATHY.

PURPOSE: To describe the presenting features and functional outcomes in a series of patients with choroidal neovascular membrane complicating BEST1-related retinopathy (Best disease and autosomal recessive bestrophinopathy). METHODS: Retrospective review of consecutive cases at a tertiary care eye hospital. Patients were identified retrospectively over an 11-year period. Records were reviewed to extract demographic as well as functional and anatomical outcome data. RESULTS: Fourteen eyes of 12 patients were identified (11 Best disease and 1 autosomal recessive bestrophinopathy). Median follow-up was 2.8 years (range 0.8-6). The median age at choroidal neovascular membrane discovery was 15.5 years (range 6-72). Choroidal neovascular membranes were active early in the disease course before vitelliruption. Seven eyes were treated with intravitreal bevacizumab, 7 eyes were monitored by observation alone. On average, patients required a single treatment (median = 1, range 1-10). The median gain in visual acuity was greater in the treated versus the observed group-0.46 versus 0.17 decimalized units of Snellen acuity, respectively (P < 0.05 Mann-Whitney U test). Although a significant reduction in central macular thickness was evident in both groups, 150 µm (treated) and 104 µm (observed), active treatment was not associated with greater thinning than observation (P > 0.05 Mann-Whitney U test). CONCLUSION: There is a high rate of spontaneous recovery of BEST1-related choroidal neovascular membrane, and overall the authors observed a gain in visual acuity associated with a reduction in central macular thickness. Active treatment, here with intravitreal bevacizumab, is associated with better functional outcomes than observation alone.

Vitamin A deficiency due to bi-allelic mutation of RBP4: There's more to it than meets the eye.

Vitamin A deficiency is the leading cause of preventable blindness in children worldwide and results in a well-recognized ocular phenotype. Herein we describe a patient presenting to the eye clinic with a retinal dystrophy and ocular colobomata. This combination of clinical signs and consanguineous pedigree structure suggested a genetic basis for the disease, a hypothesis that was tested using whole genome sequencing. Bi-allelic mutations in RBP4 were identified (c.248+1G>A), consistent with a diagnosis of inherited vitamin A deficiency. We describe a constellation of signs that appear to be characteristic for this disease, increasing clinical awareness of this rare condition.

Anisometropia and Ptosis in Patients with Monocular Elevation Deficiency.

OBJECTIVE: To determine the effect of ptosis on the refractive error in eyes having monocular elevation deficiency. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Al-Shifa Trust Eye Hospital, Rawalpindi, from January 2011 to January 2014. METHODOLOGY: Visual acuity, refraction, orthoptic assessment and ptosis evaluation of all patients having monocular elevation deficiency (MED) were recorded. Shapiro-Wilk test was used for tests of normality. Median and interquartile range (IQR) was calculated for the data. Non-parametric variables were compared, using the Wilcoxon signed ranks test. P-values of <0.05 were considered significant. RESULTS: Atotal of of 41 MED patients were assessed during the study period. Best corrected visual acuity (BCVA) and refractive error was compared between the eyes having MED and the unaffected eyes of the same patient. The refractive status of patients having ptosis with MED were also compared with those having MED without ptosis. Astigmatic correction and vision had significant difference between both the eyes of the patients. Vision was significantly different between the two eyes of patients in both the groups having either presence or absence of ptosis (p=0.04 and p < 0.001, respectively). CONCLUSION: Significant difference in vision and anisoastigmatism was noted between the two eyes of patients with MED in this study. The presence or absence of ptosis affected the vision but did not have a significant effect on the spherical equivalent (SE) and astigmatic correction between both the eyes.

Retinal Thickness and Visual Acuity in Diabetic Macular Edema: An Optical Coherence Tomography-Based Study.

OBJECTIVE: To determine the relationship between foveal (retinal) thickness and visual acuity in diabetic macular edema through optical coherence tomography (OCT) mapping software. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: The Retina Clinic of Al-Shifa Trust Eye Hospital, Rawalpindi, from August 2011 to August 2012. METHODOLOGY: Eighty eyes of 68 patients with clinical diagnosis of diabetic macular edema, based on complete ophthalmic examination, were enrolled. The best-corrected visual acuity was recorded on logMar scale. OCTimaging was performed through dilated pupil by experienced operator. Foveal thickness was determined. OCTparameters of macular thickness were analysed with baseline variables including age, duration since diagnosed with diabetes, and visual acuity. RESULTS: The mean visual acuity was 0.81 (0.2 - 1.8) logMar units. The average foveal thickness was 395.09 ±142.26 (183 - 825 µm). There was moderate correlation between foveal thickness and visual acuity (rs= 0.574, p < 0.001), absent in those who had visual acuity worse than 1 logMar. There was a weak positive association between foveal thickness and the duration of diabetes (rs=0.249, p < 0.05). There was, however, no correlation between foveal thickness and age (rs= 0.012, p=0.919). CONCLUSION: There is a moderate correlation between visual acuity and degree of foveal thickening in diabetic macular edema, hence two cannot be used interchangeably in clinical practice.

Clinical and Genetic Features of Choroideremia in Childhood.

PURPOSE: To review the functional and anatomic characteristics of choroideremia in the pediatric population, aiming to describe the earliest features of the disease and to identify biomarkers useful for monitoring disease progression. DESIGN: Retrospective case series. PARTICIPANTS: Children diagnosed with choroideremia at a single institution. METHODS: Patients were identified using an electronic patient record system. Case notes and retinal imaging (color fundus photography [CFP], spectral-domain [SD] optical coherence tomography [OCT], and fundus autofluorescence [FAF]) then were reviewed. The results of genetic testing also were recorded. MAIN OUTCOME MEASURES: Presenting symptoms, visual acuity, fundus changes (CFP, SD OCT, FAF), and CHM sequencing results. RESULTS: Twenty-nine patients were identified with a mean age at referral of 9 years (range, 3-16 years). CHM mutations were identified in 15 of 19 patients tested. Nyctalopia was the predominant symptom (66%). Five of 29 patients were asymptomatic at presentation. At the final follow-up visit (mean age, 16 years; range, 7-26 years), most maintained excellent visual acuity (mean, 0.98±0.13 decimalized Snellen acuity). The first sign of retinopathy was widespread pigment clumping at the level of the retinal pigment epithelium (RPE). This later evolved to chorioretinal atrophy, most marked in the mid-peripheral retina. Peripapillary atrophy also was an early feature and was progressive in nature. Three different zones of FAF change were visible. Persistence of the inner retinal layers, detected by SD OCT, was visible at presentation in 15 of 27 patients. Subfoveal choroidal thickness decreased with age, whereas central retinal thickness increased over a similar interval. Four patients in whom visual acuity decreased over the follow-up period recorded a reduction in central retinal thickness. CONCLUSIONS: Progressive structural changes occur at a time when central visual function is maintained. Pigmentary changes at the level of the RPE occur early in the disease course. Peripapillary chorioretinal atrophy, central retinal thickness, and subfoveal choroidal thickness are likely to be valuable in monitoring disease progression and should be considered as potential biomarkers in future therapeutic trials.

Identification of Mutations in the PRDM5 Gene in Brittle Cornea Syndrome.

BACKGROUND: Brittle cornea syndrome (BCS) is a rare autosomal recessive connective tissue disease characterized by variable combinations of corneal thinning and fragility, corneal ruptures either spontaneously or after minor trauma, blue sclerae, keratoconus, keratoglobus, and high myopia. So far, mutations in 2 genes, PRDM5 and ZNF469, have been associated with BCS. The purpose of this study is to describe novel mutations in the PRDM5 gene in patients with BCS. METHODS AND RESULTS: Using homozygosity mapping with single-nucleotide polymorphism markers followed by whole-exome sequencing, we identified a novel homozygous splice site variant (c.93+5G>A) in the PRDM5 gene in a consanguineous Pakistani family with 4 affected individuals. Reverse transcription-polymerase chain reaction analysis from lymphocyte-derived RNA failed to reveal any exon skipping because of this splice site variant. A homozygous variant (c.11T>G; p.Gln4Pro) in SEC24D also segregated with the disease in this particular family. One previously known mutation (c.974del; p.Cys325LeufsX2) was identified in a sporadic patient with BCS from Serbia. CONCLUSIONS: The current study revealed a novel mutation in the PRDM5 gene in a BCS family and recurrent mutation in a sporadic BCS patient. A variant in the SEC24D gene also segregated in the BCS family, although its role in the disease remains unclear.

Nonsyndromic Retinal Dystrophy due to Bi-Allelic Mutations in the Ciliary Transport Gene IFT140.

PURPOSE: Mutations in the ciliary transporter gene IFT140, usually associated with a severe syndromic ciliopathy, may also cause isolated retinal dystrophy. A series of patients with nonsyndromic retinitis pigmentosa (RP) due to IFT140 was investigated in this study. METHODS: Five probands and available affected family members underwent detailed phenotyping including retinal imaging and electrophysiology. Whole exome sequencing was performed on two probands, a targeted sequencing panel of 176 retinal genes on a further two, and whole genome sequencing on the fifth. Missense mutations of IFT140 were further investigated in vitro using transient plasmid transfection of hTERT-RPE1 cells. RESULTS: Eight affected patients from five families had preserved visual acuity until at least the second decade; all had normal development without skeletal manifestations or renal failure at age 13 to 67 years (mean, 42 years; median, 44.5 years). Bi-allelic mutations in IFT140 were identified in all families including two novel mutations: c.2815T > C (p.Ser939Pro) and c.1422_23insAA (p.Arg475Asnfs*14). Expression studies demonstrated a significantly reduced number of cells showing localization of mutant IFT140 with the basal body for two nonsyndromic mutations and two syndromic mutations compared with the wild type and a polymorphism. CONCLUSIONS: This study highlights the phenotype of nonsyndromic RP due to mutations in IFT140 with milder retinal dystrophy than that associated with the syndromic disease.

Variants in the ASB10 Gene Are Associated with Primary Open Angle Glaucoma.

BACKGROUND: Recently nonsynonymous coding variants in the ankyrin repeats and suppressor of cytokine signaling box-containing protein 10 (ASB10) gene were found to be associated with primary open angle glaucoma (POAG) in cohorts from Oregon and Germany, but this finding was not confirmed in an independent cohort from Iowa. The aim of the current study was to assess the role of ASB10 gene variants in Pakistani glaucoma patients. METHODS: Sanger sequencing of the coding exons and splice junctions of the ASB10 gene was performed in 30 probands of multiplex POAG families, 208 sporadic POAG patients and 151 healthy controls from Pakistan. Genotypic associations of individual variants with POAG were analyzed with the Fisher's exact or Chi-square test. RESULTS: In total 24 variants were identified in POAG probands and sporadic patients, including 11 novel variants and 13 known variants. 13 of the variants were nonsynonymous, 6 were synonymous, and 5 were intronic. Three nonsynonymous variants (p.Arg49Cys, p.Arg237Gly, p.Arg453Cys) identified in the probands were not segregating in the respective families. This is not surprising since glaucoma is a multifactorial disease, and multiple factors are likely to be involved in the disease manifestation in these families. However a nonsynonymous variant, p.Arg453Cys (rs3800791), was found in 6 sporadic POAG patients but not in controls, suggesting that it infers increased risk for the disease. In addition, one synonymous variant was found to be associated with sporadic POAG: p.Ala290Ala and the association of the variant with POAG remained significant after correction for multiple testing (uncorrected p-value 0.002, corrected p-value 0.047). The cumulative burden of rare, nonsynonymous variants was significantly higher in sporadic POAG patients compared to control individuals (p-value 0.000006). CONCLUSIONS: Variants in ASB10 were found to be significantly associated with sporadic POAG in the Pakistani population. This supports previous findings that sequence variants in the ASB10 gene may act as a risk factor for glaucoma.

Validation of Concentric Rings Method as a Topographic Measure of Retinal Nonperfusion in Ultra-Widefield Fluorescein Angiography.

PURPOSE: To validate the use of concentric rings as a method to measure topographic area of retinal nonperfusion in ultra-widefield angiography with the ischemic index method, which is the most frequently used method to measure nonperfusion in ultra-widefield angiography. DESIGN: Validation study and reliability analysis. METHODS: setting: Single-center study performed at National Institute for Health Research Moorfields Biomedical Research Centre, London, United Kingdom. STUDY POPULATION: Twenty-eight ultra-widefield angiogram images of eyes with central retinal vein occlusion. OBSERVATION PROCEDURE: The concentric rings method consists of 6 macula-centered concentric rings divided into 12 segments each. Each image was graded by 5 graders using both the concentric rings and the ischemic index methods. MAIN OUTCOME MEASURES: Agreement between the 2 methods was calculated using the intraclass correlation coefficient. Intertest agreement, intergrader agreement, test-retest reliability, and the time taken to grade using these 2 methods were compared. RESULTS: The intertest agreement between concentric rings method and ischemic index method was 0.965. The intergrader agreement was 0.910 for the concentric rings method and 0.898 with the ischemic index method. The test-retest reliability was 0.975 for the rings and 0.979 for the ischemic index. Average grading time per image was 187 s and 297 s for the concentric rings method and ischemic index method, respectively, P < .001. CONCLUSION: The concentric rings method has an "almost-perfect" intergrader agreement and intertest agreement with the ischemic index method, with a shorter grading time.

Identification of novel CYP1B1 gene mutations in patients with primary congenital and primary open-angle glaucoma.

BACKGROUND: CYP1B1 is the most commonly mutated gene in primary congenital glaucoma (PCG), and mutations have also been identified in primary open-angle glaucoma (POAG). This study was undertaken to describe mutations in CYP1B1 in patients and families with PCG and POAG from Pakistan. DESIGN: Case-control series. PARTICIPANTS: Forty families, 190 sporadic POAG cases and 140 controls from Pakistan. METHODS: Patients and healthy individuals of one consanguineous Pakistani family were genotyped with high-resolution single nucleotide polymorphism microarrays. Homozygosity mapping was performed using HomozygosityMapper. Direct sequencing of CYP1B1 gene was performed in probands of the families, sporadic POAG cases and control individuals. MAIN OUTCOME MEASURES: Mutations in the CYP1B1 gene in PCG and POAG patients. RESULTS: Homozygosity mapping in a consanguineous Pakistani family revealed one 11-Mb homozygous region encompassing the CYP1B1 gene. A homozygous CYP1B1 missense mutation (p.Arg390His) was identified in this family. Sequence analysis of CYP1B1 in 39 additional families revealed one known and three novel homozygous mutations in PCG (p.Ala288Pro, p.Asp242Ala, p.Arg355* and p.Arg290Profs*37). In POAG, one novel heterozygous missense mutation (p.Asp316Val) was identified in one family and a previously reported mutation (p.Glu229Lys) was identified in three families. Analysis of CYP1B1 in a panel of 190 sporadic POAG patients revealed three novel heterozygous variants (p.Thr234Lys, p.Ala287Pro and p.Gln362*) and three previously reported heterozygous variants (p.Gly61Glu, p.Glu229Lys and p.Arg368His). The p.Glu229Lys variant was significantly associated with POAG (P = 0.03; odds ratio 2.49). CONCLUSIONS: This study confirms that CYP1B1 mutations are associated with POAG and PCG in the Pakistani population.

Clinical course of retinoblastoma.

OBJECTIVE: To determine the clinical manifestations and results of current treatment for patients with retinoblastoma (Rb) in a tertiary care eye hospital in the north west of Pakistan. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from January 2006 and December 2009. METHODOLOGY: The data of 139 patients diagnosed as having retinoblastoma was collected. Gender, age at diagnosis, laterality, presenting sign, classification of tumour, treatment modality and outcome were noted. RESULTS: The mean age of presentation in this patients ranged from 6 to 50 months (mean: 24.05 ± 10.74 months). The most common presenting sign was leucocoria in 78 eyes (44.1%). One hundred and one (72.7%) patients had unilateral retinoblastoma. Using the International Classification of Retinoblastoma (ICRB), 135 (76.3%) eyes were placed in group-E. one hundred and twenty four (77.5%) eyes were enucleated or exenterated while globe preservation was achieved by chemoreduction and/or focal therapy in the rest of the treated eyes (n = 36, 22.5%). Twenty three (16.5%) cases were lost to follow-up before one year. Ninety two (66.2%) patients survived, being free of tumour, at least one year after the completion of treatment. CONCLUSION: Most children with Rb showed an advanced stage of tumour at the time of diagnosis. Measures to improve the rate of globe preservation and patient survival by early diagnosis and intervention are the need of the hour.

Retinal thickness evaluation in healthy eyes from north-west Punjab through optical coherence tomography.

OBJECTIVE: To determine the mean retinal thickness in healthy eyes from north-west Punjab through commercially available optical coherence tomography (OCT) mapping software, version 3.0, from the Stratus OCT (OCT3). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Al-Shifa Trust Eye Hospital, Rawalpindi, from August 2008 to February 2009. METHODOLOGY: One hundred and two eyes of 75 healthy north-west Punjabis, fulfilling inclusion criteria were enrolled from OPD of Al-Shifa Trust Eye Hospital. After informed consent, demographic detail was taken. Best-corrected Snellen visual acuity was recorded. OCT was performed by using Stratus Carl Zeiss OCT through dilated pupil by an experienced operator. The retinal thickness was divided into 9 sections and displayed as three concentric circles including a central circle at fovea (1 mm), an inner ring (3 mm) and an outer ring (6 mm), each ring being divided into four quadrants. OCT parameters of macular thickness were analysed with baseline variables including age, gender and best corrected visual acuity. RESULTS: The mean central foveal thickness (at foveola) was 166.30 ± 24.95 µm while the mean foveal thickness (in central 1000 microns) was 194.89±21.33 µm. There was no correlation between macular thickness and either age (r=0.109, p=0.275) or gender (Eta=0.128) or best corrected visual acuity (Eta=0.234). CONCLUSION: Reference values were determined for mean retinal thickness in healthy eyes from north-west Punjab through OCT. These measurements were upto 54-µm higher and upto 29 µm lower than some previously reported healthy retinal thickness values. Therefore, normative database should be determined for the population under study based on regional and ethnic differences.