La-ongsri Atchaneeyasakul

Whole Exome Sequencing in Thai Patients With Retinitis Pigmentosa Reveals Novel Mutations in Six Genes

PURPOSE To identify disease-causing mutations and describe genotype-phenotype correlations in Thai patients with nonsyndromic retinitis pigmentosa (RP). METHODS Whole exome sequencing was performed in 20 unrelated patients. Eighty-six genes associated with RP, Leber congenital amaurosis, and cone-rod dystrophy were analyzed for variant detection. RESULTS Seventeen variants (13 novel and 4 known) in 13 genes were identified in 11 patients. These variants include 10 missense substitutions, 2 nonsense mutations, 3 deletions, 1 insertion, and 1 splice site change. Nine patients with identified inheritance patterns carried a total of 10 potentially pathogenic mutations located in genes CRB1, C8orf37, EYS, PROM1, RP2, and USH2A. Three of the nine patients also demonstrated additional heterozygous variants in genes ABCA4, GUCY2D, RD3, ROM1, and TULP1. In addition, two patients carried variants of uncertain significance in genes FSCN2 and NR2E3. The RP phenotypes of our patients were consistent with previous reports. CONCLUSIONS This is the first report of mutations in Thai RP patients. These findings are useful for genotype-phenotype comparisons among different ethnic groups.

An A−71C substitution in a green gene at the second position in the red/green visual-pigment gene array is associated with deutan color-vision deficiency

We studied 247 Japanese males with congenital deutan color-vision deficiency and found that 37 subjects (15.0%) had a normal genotype of a single red gene followed by a green gene(s). Two of them had missense mutations in the green gene(s), but the other 35 subjects had no mutations in either the exons or their flanking introns. However, 32 of the 35 subjects, including all 8 subjects with pigment-color defect, a special category of deuteranomaly, had a nucleotide substitution, A−71C, in the promoter of a green gene at the second position in the red/green visual-pigment gene array. Although the −71C substitution was also present in color-normal Japanese males at a frequency of 24.3%, it was never at the second position but always found further downstream. The substitution was found in 19.4% of Chinese males and 7.7% of Thai males but rarely in Caucasians or African Americans. These results suggest that the A−71C substitution in the green gene at the second position is closely associated with deutan color-vision deficiency. In Japanese and presumably other Asian populations further downstream genes with −71C comprise a reservoir of the visual-pigment genes that cause deutan color-vision deficiency by unequal crossing over between the intergenic regions.

Neodymium:YAG laser damage threshold of foldable intraocular lenses

Purpose: To determine the energy level of the neodymium:YAG (Nd:YAG) laser that induced a 50% incidence of intraocular lens (IOL) damage in 5 foldable IOL materials. Setting: Department of Ophthalmology, Siriraj Hospital Mahidol University, Bangkok, Thailand. Methods: To simulate the condition within the capsular bag, an IOL was sandwiched between 2 rubber membranes. The front membrane had a central opening mimicking the anterior capsulotomy; the back membrane acted as the posterior capsule. The model was submerged in a water‐filled chamber. The Nd:YAG laser with an automatic focus 150 &mgr;m beyond the focus of the aiming beam was used to perform a posterior capsulotomy. Three IOLs of each of 5 foldable IOL materials were tested. One type of poly(methyl methacrylate) (PMMA) was studied as a reference. The incidence of IOL damage at various energy levels was recorded. Linear regression analysis was used to determine the 50% incidence damage threshold. Results: The 6 materials tested included 1 silicone lens (SI‐40NB, AMO), 1 hydrophobic acrylic lens (MA60BM, Alcon), 3 hydrophilic acrylic lenses (Haptibag Ang, IOLtech; ACR6D, Corneal; H60M, Bausch & Lomb), and 1 PMMA lens (LX10BD, Alcon). The 50% incidence damage threshold values were 0.37 mJ, 0.54 mJ, 0.58 mJ, 0.52 mJ, 0.66 mJ, and 0.68 mJ, respectively. Conclusions: The 50% incidence damage threshold in all the IOLs was below the energy level normally used to perform a posterior capsulotomy in clinical practice. However, setting the laser at the lowest possible energy, focusing the laser beam beyond the posterior capsule, and performing the capsulotomy early should minimize the risk of IOL damage.

Reduction of endophthalmitis rate after cataract surgery with preoperative 5% povidone-iodine.

Objective: Postoperative endophthalmitis reflects in part quality and safety aspects of cataract surgery. Preoperative 5% povidone-iodine was introduced as a quality improvement effort. This study evaluated the effect of this additional measure on the occurrence of endophthalmitis after cataract surgery. Method: Topical 5% povidone-iodine solution was applied onto the ocular surface just prior to transferring the patient into the operative theater for cataract surgery. Other prophylactic measures were allowed to continue as before. Patients developing postoperative intraocular inflammation and undergoing intravitreal antibiotic injection were included as occurrences of endophthalmitis. Alteration in endophthalmitis rate was analyzed using a ‘p control chart’ of a statistical process control method. The incidence in the povidone-iodine-receiving group was compared to those before implementation and concurrent nonreceiving groups. Result: The postoperative endophthalmitis rate showed a significant reduction after introduction of povidone-iodine. A year before, 9 of 3,052 eyes developed endophthalmitis (0.294%). After introduction, this occurred in 4 of 4,089 eyes receiving povidone-iodine (0.097%) and 1 of 502 nonreceiving eyes (0.199%) in the following 16 months. Despite the apparent lower rate, comparison between groups was not statistically significant. Moderate to severe but tolerable eye irritation after application was reported in 6.6%. No other adverse events were detected. Conclusion: Topical preoperative 5% povidone-iodine contributed an additional effect to the reduction of the postoperative endophthalmitis rate after cataract surgery. This measure was rather safe to apply as a prophylaxis against endophthalmitis in cataract surgery.

Applicability of American and British Criteria for Screening of the Retinopathy of Prematurity in Thailand

PurposeThe aim of this study was to verify the applicability of standard guidelines for the screening of retinopathy of prematurity (ROP) and to determine the appropriate criteria for Thai neonates.MethodsRecords of ROP screening of infants born in our hospital between 1995 and 2000 with a birth weight below 2000 g or a gestational age of less than 36 weeks were studied. Criteria to screen infants with a birth weight below 1500 g or a gestational age of less than 28 weeks in the American guidelines and similar birth weight but a gestational age of less than 31 weeks in the British recommended guidelines were applied and evaluated in terms of sensitivity and specificity. Criteria reaching 100% sensitivity with the maximum specificity were deemed appropriate.ResultsOf the 514 screened infants, 33 had developed stage 2+ ROP and beyond. The mean ± SD birth weight and gestational age were 1046 ± 257 (710–1680 g) and 29.2 ± 2.5 weeks (24–35 weeks), respectively. The age at intervention was 6–16 weeks. Sensitivity for both American and British guidelines was 93.9%. By screening infants with birth weights below 1500 g or gestational age less than 33 weeks, we could achieve 100% sensitivity with 18.3% specificity. We decided that the initial examination should be performed 4–6 weeks after birth. By applying these criteria to 62 referred cases we also were able to include in the screening all cases of concern in this group.ConclusionsRegional criteria for ROP screening is required and should be evaluated periodically and modified accordingly. Jpn J Ophthalmol 2004;48:50–53

The unique characteristics of Thai Leber hereditary optic neuropathy: analysis of 30 G11778A pedigrees

AbstractLeber hereditary optic neuropathy (LHON) is characterized by acute or subacute bilateral visual loss, and affects mostly young males. The most common mitochondrial DNA mutation responsible for LHON worldwide is G11778A. Despite different genetic backgrounds, which are believed to influence the disease expression, most features of LHON are quite common in different populations. However, there seem to be a few ethnic-specific differences. Analyses of our 30 G11778A LHON pedigrees in Thailand showed some characteristics different from those of Caucasians and Japanese. In particular, our pedigrees showed a lower male to female ratio of affected persons (2.6:1) and much higher prevalence of G11778A blood heteroplasmy (37% of the pedigrees contained at least one heteroplasmic G11778A individual). Heteroplasmicity seemed to influence disease manifestation in our patients but did not appear to alter the onset of the disease. The estimated overall penetrance of our G11778A LHON population was 37% for males and 13% for females. When each of our large pedigrees were considered separately, disease penetration varied from 9 to 45% between the pedigrees, and also varied between different branches of the same large pedigree. Survival analysis showed that the secondary LHON mutations G3316A and C3497T had a synergistic deleterious effect with the G11778A mutation, accelerating the onset of the disease in our patients.

Treatment of Epidemic Keratoconjunctivitis with 2% Povidone–Iodine: A Pilot Study

PURPOSE The purpose of this study was to analyze the outcome of treating epidemic keratoconjunctivitis (EKC) with 2% povidone-iodine (PVP-I) solution. METHODS A prospective, interventional, uncontrolled study was performed in participants diagnosed with EKC. PVP-I was applied to the affected eyes 4 times a day for a week. Participants were informed about transient eye stinging and discoloration after application. Drug discontinuation was allowed for early recovery or encountering any adverse effects. Data collection included history, symptoms, and signs at the initial presentation and at 1 week. Main outcomes were the recovery rate within a week of treatment and drug tolerability. RESULTS Of 172 enrolled, 61 participants completed the study. EKC occurred bilaterally in 40 participants (66%). Single eye from each participant was included for analysis. The mean (standard deviation) time elapsed before treatment was 2.1 (1.46) days. The recovery rate within a week of treatment was 77% (95% confidence interval, 65.1-85.8). Twenty-eight participants (45.9%) recovered within a week after the onset. Application of PVP-I was sustained until recovery or completing a 7-day trial in 78.7%. No severe ocular or systemic adverse effects have been reported related to this treatment. CONCLUSIONS Ocular application of 2% PVP-I was tolerable. This measure successfully relieved ocular discomfort from EKC in 3 quarters of the study group within a week. A randomized, controlled trial is required to verify the benefit of this measure.

Novel and De-novo Truncating PAX6 Mutations and Ocular Phenotypes in Thai Aniridia Patients

Purpose: To describe the ophthalmic findings and mutation analyses of the PAX6 gene in Thai aniridia patients. Methods: Ten patients from six unrelated families underwent a comprehensive ophthalmic examination. Mutations in the PAX6 gene were screened by single-strand conformational polymorphism (SSCP) and direct DNA sequencing of the SSCP variants. Results: Seven patients developed cataracts and six developed glaucoma. Mutation analysis demonstrated four different truncating mutations, two of which were de novo. These included one novel insertion/deletion mutation (c.474del12insGA in exon 5) and three nonsense mutations. R203X and R240X are common recurrent mutations, while Q277X in exon 10 is novel. All mutations resulted in loss of function of the PAX6 protein. Conclusion: Our data confirm inter- and intrafamilial variable phenotypic manifestations of which the underlying mechanisms may be haploinsufficiency or dominant-negative mutation.

A Novel H572R Mutation in the Transforming Growth Factor-β-Induced Gene in a Thai Family with Lattice Corneal Dystrophy Type I

PurposeTo describe a large Thai family with lattice corneal dystrophy (LCD) type I and to determine whether this LCD is associated with mutations within the transforming growth factor-β-induced (TGFBI) gene.MethodsA six-generation family with LCD type I was identified and diagnosed on the basis of clinical and/or histopathologic evaluation. Visual acuity testing and slit-lamp biomicroscopic evaluation were carried out and corneal photography was documented. All 17 exons and flanking intron sequences of the TGFBI gene were sequenced.ResultsThirty-three participants demonstrated LCD in both eyes, most of which was symmetrical. Age at onset of decreased vision was the mid- to late twenties. Visual acuity varied from 6/6 to no light perception. Two patients, 74 and 42 years of age, demonstrated a thick yellowish plaque covering the corneal surfaces. DNA sequencing revealed a heterozygous mutation in exon 13 (A1762G), changing histidine to arginine at codon 572 (H572R). Ten of 42 clinically unaffected family members, all under 25 years of age, exhibited the same mutation.ConclusionsThis is the first report of a molecular analysis of LCD type I in Thai patients. The novel mutation identified is associated with distinct phenotypes and later onset of the disease compared with the more common R124C mutation. Jpn J Ophthalmol 2006;50:403–408

Prognostic factors and treatment outcomes of retinoblastoma in pediatric patients: a single-institution study

PurposeSince 1997, our institute has used neoadjuvant chemotherapy for intraocular retinoblastoma. However, some of the patients showed signs of recurrence months to years later. We therefore attempted to determine the prognostic factors of treatment outcomes and survival in our patients.MethodsWe reviewed 90 patients treated from 1997 to 2006. The following information was recorded: demographic and ophthalmological data, clinical classification, histopathological data, and treatment methods and outcomes.ResultsEnucleation was avoided in two of 57 eyes in the unilateral group. Sixteen of 54 eyes in the bilateral group were salvaged by systemic chemotherapy with local treatment. There was no difference in histopathological findings between the two groups. Nine of 57 patients in the unilateral group demonstrated poor outcomes, compared with four of 27 in the bilateral group. Significant poor prognostic factors for survival were optic nerve head invasion, orbital involvement, abnormal results on bone marrow aspiration, lumbar puncture, bone scan, and group E or F classification.ConclusionsThe 15% mortality rate in our patients is slightly higher than that reported in developed countries. Delayed diagnosis and treatment is the main cause of avoidable deaths. Improving education of both clinicians and parents would increase survival rates in this potentially fatal disease.