Keratoconus in Thai population - a cross-sectional hospital-based study.

Background: Studies in the epidemiology of keratoconus are limited in Southeast Asia. A study on the prevalence and characteristics of keratoconus in the Thai population could give a general idea of its impact. Objectives: To study keratoconus prevalence in patients seeking refractive surgery and analyze the characteristics of keratoconus. Methods: Medical records from April 2015 to August 2018 were retrospectively reviewed. Keratoconus and keratoconus suspect prevalence in patients seeking laser vision correction were calculated. The characteristics of keratoconus patients were reviewed. The Amsler-Krumeich classification was used to determine the stages. Topographically, the types of cones were categorized into oval, nipple, pellucid marginal degeneration (PMD)-like, and astigmatic types. Results: Keratoconus and keratoconus suspect prevalence were 1.66% and 0.68%, respectively. Out of the affected patients, 73.8% were male. The mean age at diagnosis was 25.25 ± 8.35 years. The presenting symptoms were blurred vision (87%) and itching (47%). Stage 1 was predominant, found in 39% of patients (followed by stages 2, 4, and 3, respectively). Ocular findings comprised the Munson sign (14.63%), the Rizutti sign (6.94%), Fleischer ring (28.14%), Vogt striae (24.95%), corneal scar (8.63%), prominent corneal nerve (2.81%), and corneal staining (7.69%). Mean uncorrected visual acuity (logarithm of the minimum angle of resolution [logMAR]) was 0.88 ± 0.64. Mean corrected visual acuity (logMAR) was 0.40 ± 0.49. Mean Q-value was -0.92 ± 0.63. The thinnest pachymetry was 459.39 ± 56.96 microns. The mean keratometry was 49.7 ± 6.64 diopters. Topographically, the types of cones were oval (57%), astigmatic (33%), PMD-like (5%), and nipple type (4%). Conclusions: Keratoconus prevalence among Thai patients seeking refractive surgery was 1.66%. Most patients were male and presented with the disease at a mild bilateral stage in their second decade of life.

Prevalence of Human Papillomavirus Genotypes in Pterygia from Thai Individuals.

PURPOSE: Pterygium, a common ocular growth, has an unknown pathogenesis and aetiology. Environmental factors such as ultraviolet light, genetic factors and viral infections may be implicated in the development of pterygia. Human papillomavirus (HPV), an oncogenic virus, has previous been detected in individuals with pterygia. The aim of this study was to assess the prevalence of HPV genotypes in pterygia from Thai individuals. METHODS: DNA was extracted from 389 pterygia. HPV was detected by nested PCR and HPV genotyping was conducted using reverse hybridization. The DNA sequences of HPV-L1 genes were analyzed. RESULTS: HPV was detected in only 6.8% (25/389) of pterygia from Thai individuals. The majority (16/25, 64%) of strains were genotyped as HPV-16 and the remainder (9/25, 36%) could not be typed. Four pterygia showed evidence of coinfection by HPV-16 and either HPV-18 (2/25, 8%) or HPV-58 (2/25, 8%). Nine of 11 samples showed the same HPV-16 L1 gene sequence that was identical to a HPV-16 reference sequence in GenBank. The remaining two samples each bore silent single nucleotide mutations (T1078G and T1081A) that did not result in amino acid changes. CONCLUSION: HPV, especially HPV-16, may be one of the pathogens causing pterygia in Thai individuals. Genotyping data suggested that HPV-16 from pterygia may be similar in sequence to HPV-16 causing cervical cancer.

Association of HLA polymorphisms and acetaminophen-related Steven-Johnson syndrome with severe ocular complications in Thai population.

BACKGROUND/AIMS: To investigate the association of genetic polymorphisms of human leucocyte antigens (HLA) class I and II genes with acetaminophen-related Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) who developed severe ocular complications (SOC) in the Thai population. METHODS: A prospective case-control study including 20 unrelated Thai acetaminophen-related SJS/TEN patients with SOC and 60 Thai healthy volunteers, recruited at three university hospitals in Bangkok, Thailand, from September 2014 to August 2019. HLA genes were analysed using PCR amplification followed by hybridisation with sequence-specific oligonucleotide (SSO) probes with bead-based typing kits. The carrier and gene frequencies of individual HLA alleles in patients were compared with those in control volunteers based on dominant assumption using Fisher's exact test. RESULTS: Among HLA class I polymorphisms, HLA-A*33:03, HLA-B*44:03 and HLA-C*07:01 were significantly associated with acetaminophen-related SJS/TEN and SOC with high ORs (95% CI, corrected p value; Pc) in carrier frequency of 5.4 (1.8 to 16.3, Pc=0.0274), 9.0 (95% CI 2.7 to 30.4, Pc=0.0034), and 9.3 (2.8 to 30.2, Pc=0.0022), respectively. There were no significant HLA class II associations with the disease after corrected for a total number of alleles tested. CONCLUSION: HLA-B*44:03 was strongly associated with acetaminophen-related SJS/TEN patients who developed SOC in Thai population. In addition, we also found moderate to strong associations with HLA-A*33:03 and HLA-C*07:01 suggesting their potential roles in the pathogenesis of SOC in acetaminophen-related SJS/TEN.

Clinical Characteristics, Histopathology, and Treatment Outcomes of Pythium Keratitis: A Retrospective Cohort Study.

PURPOSE: To identify factors associated with the prognosis in Pythium keratitis. PATIENTS AND METHODS: The medical records of 25 patients (26 eyes) diagnosed with Pythium keratitis at a referral institution were reviewed. The demographic and clinical characteristics, treatment, microbiological diagnosis, histopathological features, and outcomes were recorded. The histopathological specimens were reviewed. The patients were divided into a globe removal group and a globe salvage group. Univariate analysis was used to identify factors associated with poor outcomes. RESULTS: Fifteen eyes (57.7%) were removed. Patients in the globe removal group were on average 16.4 years older (95% CI 6.98 to 25.88) than those in the globe salvage group, received the first medication (either topical antifungals or antibiotics) later than one day after the onset of symptoms (RR = 2.75, 95% CI 1.18 to 6.42), and had a maximal diameter of the infiltration area ≥6 mm (RR = 3.14, 95% CI 1.17 to 8.45). The globe removal group showed satellite, multifocal, or total corneal infiltration patterns (RR = 2.82, 95% CI 1.03 to 7.74) and a hypopyon (RR = 3.43, 95% CI 1.26 to 9.35) as risk factors. The histopathological examination showed a higher density of Pythium in the globe removal group than the globe salvage group (median 376 (interquartile range 323, 620) versus 107 (interquartile range 16, 260) hyphae per high power field; P = 0.035). CONCLUSION: The risk of globe removal in patients with Pythium keratitis increased with age, delayed initial topical antifungal or antibiotic treatment, advanced disease at presentation, and dense Pythium hyphae infiltration of the cornea. Early recognition and treatment are critical to successfully eradicate the infection.

Trinucleotide repeat expansion in the transcription factor 4 (TCF4) gene in Thai patients with Fuchs endothelial corneal dystrophy.

PURPOSE: To evaluate the association of single nucleotide polymorphisms (SNPs) and the intronic expansion of a trinucleotide repeat (TNR) in the TCF4 gene with Fuchs endothelial corneal dystrophy (FECD) in a Thai population. METHODS: In total, 54 Thai FECD patients and 54 controls were recruited for the study. Five SNPs (rs613872, rs2123392, rs17089887, rs1452787, and rs1348047), previously reported to be associated with FECD, were genotyped by direct sequencing. The repeat length was determined by direct sequencing of PCR-amplified DNA (a short tandem repeat; STR assay) and by triplet repeat primed PCR (TP-PCR). RESULTS: Only one of the 54 patients with FECD harboured rs613872 (1.9%). Four SNPs (rs2123392, rs17089887, rs1452787, and rs1348047), which are not rare polymorphisms in the Thai population, were found in approximately half of the patients. Of the 54 patients, 21 (1 homozygous and 20 heterozygous patients; 39%) harboured a TNR ≥ 40, while 33 patients (61%) harboured a TNR < 40. CONCLUSIONS: The association of TNR expansion in TCF4 with FECD is shown for the first time in the Thai population. The intronic TNR expansion identified in various ethnic groups underlines the importance of expansion as a potent pathophysiological cause of FECD.

A Survey of Surgical Techniques in Pterygium, Thailand 2016.

BACKGROUND: Pterygium causes a significant ocular disturbance which usually requires surgical removal; however, recurrence of pterygium after surgery frustrates both patients and surgeons. This survey aimed to determine the current surgical approaches in primary and recurrent pterygium, and the ideal surgical techniques among Thai ophthalmologists. METHODS: Questionnaires were sent to 1150 ophthalmologists who are members of Royal College of Ophthalmologists of Thailand (RCOPT). A survey was conducted between 21 September and December 21, 2016. RESULTS: 438 of 515 responded questionnaires were valid. The highest number of the respondents applied the bare sclera technique (BST) (37.4%) and conjunctival autograft transplantation (CAGT, 44.9%) in primary pterygium and recurrent pterygium, respectively. The recurrence was the most reported late postoperative complication. An ideal technique for primary pterygium surgery was CAGT (42.4%), whereas amniotic membrane transplant (AMT) with adjuvant therapy (27.4%) was most selected for recurrent pterygium. Around half of the respondents currently applied the ideal techniques in their practice. The inaccessible and unaffordable amniotic membranes or fibrin glues (58%) concerning about complications (26%), inexperience in surgical procedures (25%), large number of patients in the surgery waiting list, prolonged surgical time, and need for conjunctiva preservation in glaucoma patients were reported as the obstacles to the ideal techniques. CONCLUSIONS: BST and CAGT were the most selected surgical techniques for primary and recurrent pterygium, respectively. Better provision and distribution of amniotic membranes and fibrin glue along with training courses would promote the ideal surgical techniques.

Association of IKZF1 SNPs in cold medicine-related Stevens-Johnson syndrome in Thailand.

PURPOSE: Our meta-analysis of several ethnic groups (Japanese, Korean, Indian, Brazilian) revealed a significant genome-wide association between cold medicine-related SJS/TEN (CM-SJS/TEN) with severe ocular complications (SOC) and IKZF1 SNPs, suggesting that IKZF1 might be a potential marker for susceptibility to CM-SJS/TEN with SOC. In this study, we examined the association between CM-SJS/TEN with SOC and the IKZF1 SNPs in the Thai population. METHODS: 57 CM-SJS/TEN with SOC and 171 control samples were collected at Chulalongkorn University and Mahidol University. Genomic DNA samples were genotyped for the IKZF1 SNPs at Kyoto Prefectural University of Medicine in Japan using the TaqMan SNP genotyping assay. RESULTS: The four SNPs previously reported to be associated with CM-SJS/TEN with SOC in the Japanese were examined in the Thai samples. Although the number of Thai cases (n = 57) was small, a significant association between CM-SJS/TEN with SOC and IKZF1 SNPs which included rs4917014 (T vs G, OR = 2.9, p = 0.0012, Pc = 0.0049), rs4917129 (T vs C, OR = 2.8, p = 0.0026, Pc = 0.010) and rs10276619 (G vs A, OR = 1.8, p = 0.012, Pc = 0.048) was identified. CONCLUSION: In addition to the Japanese, Korean and Indian populations, Thai cases with CM-SJS/TEN and SOC were significantly associated with IKZF1 SNPs. With our previous report of the critical role of IKZF1 in mucocutaneous inflammation, these results suggest that IKZF1 is important in the pathogenesis of CM-SJS/TEN with SOC.

Topometric Indices And Corneal Densitometry Change After Corneal Refractive Surgery Combined With Simultaneous Collagen Crosslinking.

PURPOSE: To show the alteration of tomography, topometric indices and corneal densitometry after corneal refractive surgery combined with collagen crosslinking. PATIENTS AND METHODS: All medical records of patients undergoing corneal refractive surgery with simultaneous collagen crosslinking during April 2015 and August 2018 were retrospectively reviewed. Corneal tomography, higher-order aberrations (HOA), topographic indices and corneal densitometry were evaluated. All the data at 1 month, 3 months and 6 months were compared to baseline value. All complications were noted. P value less than 0.05 was considered statistically significant. RESULTS: Medical records of fourteen patients (twenty-five eyes) were reviewed. HOA increased at all time points (p < 0.05). Keratoconus index and central keratoconus index decreased, whereas index of surface variance, index of vertical asymmetry, index of height decentration and the minimum of radius of curvature increased at all time points (p < 0.05). Index of height asymmetry increased at 3 and 6 months (p < 0.05). Corneal densitometry at anterior layer of 0-10 mm zone and center layer of 0-6 mm zone increased at 1 and 3 months (p < 0.05). At 6 months, the densitometry at 0-6 mm zone returned to baseline level. However, at 6 months, at anterior and center layer of 6-10 mm zone, the densitometry values were still more than preoperative values (p < 0.05). There was one case of bacterial keratitis. CONCLUSION: After the corneal refractive surgery combined with collagen crosslinking, the HOA and corneal densitometry increased. Topographic indices showed conflicting results.

Association between HLA-B*44:03-HLA-C*07:01 haplotype and cold medicine-related Stevens-Johnson syndrome with severe ocular complications in Thailand.

BACKGROUND: Polymorphisms in human leucocyte antigen (HLA) class I genes have been found to be associated with cold medicine (CM)-related Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with severe ocular complications (SOC). Because ethnic differences in genetic predisposition to SJS/TEN among different populations have been proposed, we focused on Thai patients and investigated the association between HLA class I genotypes and CM-SJS/TEN with SOC. METHODS: This multicentre case-control study was conducted between September 2014 and August 2017. Seventy-one Thai patients with SJS/TEN with SOC and 159 healthy Thai controls were enrolled. HLA typing was performed. Genetic relationships were analysed using Fisher's exact test. RESULTS: Of 71 patients with SJS/TEN with SOC (28 male, 43 female), 49 (69%) had a history of taking cold medications prior to SJS/TEN onset. The mean age of onset was 26.7±17.1 years (range, 2-77 years). HLA-B*44:03 (OR, 7.2, p=5.5×10-6, pc=1.1×10-4) and HLA-C*07:01 (OR, 6.1, p=7.1×10-6, pc=1.1×10-4) showed significant positive associations with Thai patients with CM-SJS/TEN with SOC. Additionally, 17 of 49 patients with CM-SJS/TEN with SOC (34.7%) significantly harboured the HLA-B*44:03 and HLA-C*07:01 haplotype compared with only 11 of 159 healthy controls (6.9%) (OR=7.1, p=5.5×10-6). CONCLUSIONS: HLA-B*44:03-HLA-C*07:01 haplotype is a potential risk factor for CM-SJS/TEN with SOC in the Thai population. This study supports that HLA-B*44:03 might be a common marker for CM-SJS/TEN with SOC in Eurasia populations, including European, Indian, Japanese and Thai.

Descemet's scroll in syphilitic interstitial keratitis: a case report with anterior segment evaluation and a literature review.

PURPOSE: To present a case of syphilitic interstitial keratitis with Descemet's scrolls, as well as its characteristic findings in an anterior segment investigation in relation to the histopathologic findings from a literature review. CASE PRESENTATION: A case report of a 64-year-old woman with syphilitic infection presented with band keratopathy and retrocorneal scrolls. Slit-lamp photography, confocal microscopy, anterior segment optical coherence tomography (AS-OCT), and ultrasound biomicroscopy were performed. Four previous reports were reviewed to describe the pathogenesis, natural history, and histopathologic and immunohistologic findings of the Descemet's scroll. RESULTS: The spectacle-corrected visual acuity was 20/50 and 20/30 in the right and left eyes, respectively. The scrolls appeared as a translucent web extending from Descemet's membrane into the anterior chamber. Confocal microscopy showed decreased endothelial cell density, pleomorphism, polymegathism, and hyperreflective fibrocellular rods with central hollow. The AS-OCT and ultrasound biomicroscopy showed rod-shaped retrocorneal scrolls. The corneal thickness was 494 microns, as measured by AS-OCT. The corneal lesion remained stable during the 6-year follow-up period without the need for keratoplasty, while the previous literature reported spontaneous and postoperative corneal decompensation. CONCLUSION: We present a case of syphilitic interstitial keratitis with rare Descemet's scrolls featuring relatively good visual acuity. Although we did not obtain the corneal tissue for examination, the anterior segment investigation provides insight into the underlying histopathology and natural disease history. The central hollow and cellular component seen during confocal microscopy might correspond to the amorphous core and the abnormal endothelial cells in the histopathologic findings. Failure to detect the corneal endothelium due to stromal opacity in these cases is possible, however, compromised endothelium may present.

Major single nucleotide polymorphisms in polypoidal choroidal vasculopathy: a comparative analysis between Thai and other Asian populations.

PURPOSE: To investigate the association in a Thai population between the major age-related macular degeneration (AMD) susceptibility loci, Y402H and I62V in the complement factor H (CFH) and A69S in the age-related maculopathy susceptibility 2 (ARMS2) genes, and polypoidal choroidal vasculopathy (PCV). METHODS: A case-control study included 97 PCV cases and 102 age- and gender-matched controls without any retinopathy. The genotypic profiles of the three polymorphisms were obtained using a real-time polymerase chain reaction assay. The allelic and genotypic association between the polymorphisms and PCV were compared with those from the compiled data of other Asian populations reported previously. RESULTS: Strong associations between the Y402H, I62V, and A69S polymorphisms and PCV were observed in the present study (P = 0.002, 0.003, and 0.0008 respectively) and in the compiled data (P < 0.0001 for all three polymorphisms). The risk allele frequencies of the polymorphisms in PCVs and in controls from the present study (15.0% and 5.4% for Y402H, 71.7% and 57.4% for I62V, and 54.1% and 37.3% for A69S respectively) were also comparable with the frequencies from the compiled data (10.3% and 6.4% for Y402H, 75.2% and 58.3% for I62V, and 56.8% and 36.8% for A69S respectively). The genotype distribution for each polymorphism was also comparable in both datasets. CONCLUSION: The findings of this study support a significant genetic association between the major AMD susceptibility genes and PCV across Asian populations. This suggests that AMD and PCV, despite different phenotypic manifestation, may share common genetic risk factors.