Long-Term Review of Penetrating Keratoplasty: A 20-Year Review in Asian Eyes.

PURPOSE: To review the long-term outcomes of optical, therapeutic and tectonic forms of penetrating keratoplasty over a 20-year period in Asian eyes. DESIGN: Prospective cohort study involving the Singapore Corneal Transplant Study (SCTS). METHODS: All penetrating keratoplasties (PK) performed at the Singapore National Eye Centre (SNEC) from January 1991 to December 2010 were analyzed using records from the computerized database of the SCTS. This database includes preoperative, intraoperative, and postoperative patient data and donor cornea data. Only primary grafts were included. Patient demographics, donor cornea source, indications for grafting, complications, graft survival rate, and causes of graft failure were analyzed. RESULTS: A total of 1,206 primary PKs were performed. The mean age of the patients was 55 years (range: <1-101 years). The overall corneal graft survival rates at 1, 5, 10, 15, and 20 years were 91%, 66.8%, 55.4%, 52%, and 44%, respectively. For optical grafts, pseudophakic bullous keratopathy, postinfectious corneal scarring and thinning and keratoconus were the most common diagnoses. Graft survival for optical grafts was significantly better than therapeutic and tectonic grafts at all time points. Multivariate analysis suggested that a younger donor cornea age and higher donor endothelial cell count are associated with better long-term graft survival for optical grafts. Irreversible allograft rejection and late endothelial failure accounted for more than 60% of graft failures. CONCLUSIONS: Graft survival decreased over time from 91% at 1 year to 44% at 20 years' follow-up. Allograft rejection and late endothelial failure accounted for more than 60% of graft failures.

A multiethnic genome-wide analysis of 44,039 individuals identifies 41 new loci associated with central corneal thickness.

Central corneal thickness (CCT) is one of the most heritable human traits, with broad-sense heritability estimates ranging between 0.68 to 0.95. Despite the high heritability and numerous previous association studies, only 8.5% of CCT variance is currently explained. Here, we report the results of a multiethnic meta-analysis of available genome-wide association studies in which we find association between CCT and 98 genomic loci, of which 41 are novel. Among these loci, 20 were significantly associated with keratoconus, and one (RAPSN rs3740685) was significantly associated with glaucoma after Bonferroni correction. Two-sample Mendelian randomization analysis suggests that thinner CCT does not causally increase the risk of primary open-angle glaucoma. This large CCT study explains up to 14.2% of CCT variance and increases substantially our understanding of the etiology of CCT variation. This may open new avenues of investigation into human ocular traits and their relationship to the risk of vision disorders.

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.

Accounting for Ethnicity-Related Differences in Ocular Surface Integrity as a Step Toward Understanding Contact Lens Discomfort.

Contact lens discomfort is a common problem that can lead to unsuccessful or limited contact lens wear. Although many factors may contribute to contact lens discomfort, limited research has explored the influence of ethnicity-related differences in the anatomy and physiology of the ocular surface. Therefore, we performed a search of the literature in PubMed using key words related to "ocular surface" paired with the terms "race" and "ethnicity." The goal of this review was to determine potential areas of research regarding ethnicity differences, particularly between Asian and non-Asian eyes, in ocular surface integrity to advance our understanding of contact lens discomfort.

Techniques for Learning Descemet Membrane Endothelial Keratoplasty for Eyes of Asian Patients With Shallow Anterior Chamber.

PURPOSE: To describe several essential surgical techniques that overcome difficulties in performing Descemet membrane endothelial keratoplasty (DMEK) for inexperienced surgeons, especially those who perform DMEK on eyes of Asian patients. METHODS: Nine eyes of 9 Asian patients with bullous keratopathy who underwent DMEK were analyzed retrospectively. All patients were given a diuretic such as D-mannitol or acetazolamide shortly before surgery, with retrobulbar anesthesia and a Nadbath facial nerve block. Core vitrectomy before DMEK was performed in several cases in which a high vitreous pressure during surgery was predicted. The donor graft was stained with trypan blue, and a 25-G anterior chamber maintenance cannula was used to maintain the anterior chamber depth during graft insertion in all eyes. RESULTS: The cornea became clear in all eyes. The best spectacle-corrected visual acuity had improved significantly 6 months after the surgery compared with preoperative values (P = 0.026). The corneal endothelial cell density was 1371 cells per square millimeter at postoperative 6 months. CONCLUSIONS: Although DMEK is technically difficult, especially for inexperienced surgeons who operate on eyes of Asian patients, controlling anterior chamber pressure using various manipulations may help to prevent iatrogenic primary graft failure and lead to successful DMEK.

Five-Year Graft Survival Comparing Descemet Stripping Automated Endothelial Keratoplasty and Penetrating Keratoplasty.

PURPOSE: To compare 5-year graft survival after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) in Asian eyes. DESIGN: Prospective, nested, cohort study. PARTICIPANTS: Consecutive patients who underwent DSAEK (423 eyes) or PK (405 eyes) for Fuchs' endothelial dystrophy (FED) or bullous keratopathy (BK). METHODS: Clinical data and donor and recipient characteristics were recorded from our prospective cohort from the Singapore Corneal Transplant Registry. All surgeries were performed by the corneal surgeons at our center, which included cases performed or partially performed by corneal fellows in training under direct supervision. MAIN OUTCOME MEASURES: Five-year cumulative graft survival. RESULTS: Overall mean age was 67.8±9.8 years, and 50.1% of patients were men. There were no significant differences in age (P = 0.261) or gender (P = 0.78) between PK and DSAEK groups in our predominantly Chinese (76.6%) Asian cohort, with more BK compared with FED (68.1% vs. 31.9%; P < 0.001). Overall 5-year graft survival was superior for DSAEK compared with PK (79.4% vs. 66.5%; P < 0.001, log-rank test). Median 5-year percent endothelial cell density loss was significantly greater in PK compared with DSAEK (60.9% vs. 48.7%; P = 0.007). Cox regression analysis revealed that BK was a significant factor associated with graft failure (hazard ratio [HR], 3.30; 95% confidence interval [CI], 2.05-5.33; P < 0.001), and PK was more likely to fail compared with endothelial keratoplasty (HR, 1.61; 95% CI, 1.08-2.41; P = 0.02) adjusting for confounders such as recipient age, gender, and donor factors. Five-year cumulative incidence of complications such as graft rejection (P < 0.001), epitheliopathy (P < 0.001), suture-related corneal infections (P < 0.001), and wound dehiscence (P = 0.002) were greater in the PK group compared with the DSAEK group. CONCLUSIONS: In Asian eyes from the same study cohort with standardized surgical and postoperative regimes, 5-year graft survival was superior for DSAEK compared with PK in eyes with FED and BK.

Racial Disparities in Corneal Transplantation Rates, Complications, and Outcomes.

Corneal transplantation is a common type of tissue transplantation that aims to improve vision or relieve pain. Given the immune privilege of the cornea, the primary graft often has a high success rate, approaching 90%. Despite the good overall outcome of corneal transplantation in various studies, the individual graft survival rate varies, depending on the preoperative diagnosis and donor and recipient factors. Race and ethnicity have been shown to be important in other types of organ transplantation. The aim of this study was to review the available ophthalmic literature regarding any differences in rates and outcomes of corneal transplantation based on ethnicity and race. A small body of evidence suggests that race might be an important risk factor for graft rejection and graft failure. More robust studies are needed to clarify these associations.

Acute corneal hydrops in keratoconus: a national prospective study of incidence and management.

PurposeTo determine incidence and management of acute corneal hydrops in the UK.MethodsWe used the BOSU report card system to survey cases of acute corneal hydrops in patients with keratoconus that occurred in the UK between November 2009 and December 2010. Ophthalmologists who reported a case were sent an initial questionnaire, with a follow-up questionnaire after 6 months. We collected information on the demographics, complications, changes in visual acuity, and management. The 2011 National Census was used as a source for population and ethnicity in the UK.ResultsThere were 73 incident cases of acute corneal hydrops, with a response to the initial questionnaire for 64 (88%) patients and follow-up data at 6 months for 57 (78%) patients. For the 64 confirmed cases the median (interquartile range) age of onset was 31.9 (23.2, 41.3) years and 48 (75%) of the cases occurred in males. A total of 42 (66%) patients were white, 14 (22%) were South Asian, and 7 (11%) were black. The proportion of South Asian and black patients with acute corneal hydrops was significantly higher than in the general population (P<0.001). The minimum estimated annual incidence of acute corneal hydrops in patients with keratoconus was estimated to be 1.43 (1.10, 1.83) per 1000. At 6 months following acute corneal hydrops a decision to proceed with keratoplasty had been made for 12 (20.3%) patients.ConclusionsThis is the first population-based estimate of the incidence of acute corneal hydrops in keratoconus.

Treatment adherence after penetrating corneal transplant in a New Zealand population from 2000 to 2009.

PURPOSE: The aim of this study was to evaluate the extent of nonadherence after penetrating keratoplasty in Auckland, New Zealand, over a 10-year period and to identify predictive variables. METHODS: The New Zealand National Eye Bank records were analyzed for the decade January 1, 2000, to December 31, 2009, inclusive. Variables evaluated included age, gender, ethnicity, proximity to treatment center, level of deprivation, indication for surgery, previous ocular surgery. The number of scheduled appointments offered and attended by each patient was recorded. Outcome measures were appointment compliance and 2-year follow-up completion. RESULTS: Over the study period, 1055 corneal transplant procedures were identified. After applying exclusion criteria, data from 695 penetrating keratoplasty procedures were included in the study. Two-year follow-up information was available for 91.4%, of which 87.8% survived and 77 (12.1%) failed. Over the study period, 1065 (10.5%) appointments were not attended by patients. Appointment compliance was good in 68.5%, moderate in 26.3%, and poor in 4.9%. Maori and Pacific Island ethnicities were observed to be associated with the lowest level of attendance, whereas European and Indian ethnicities were the most likely to complete follow-up. Rates of appointment compliance were greater at private treatment centers (P = 0.009) and inversely associated with proximity to treatment center (P < 0.0001). CONCLUSIONS: The rate of nonattendance reported in this study is considerably higher than that observed in other forms of organ transplantation. Both ethnic and socioeconomic factors seem to have a significant influence on attendance compliance. Strategies to improve adherence should take these factors into account.

Contact lens care solutions: a pilot study of ethnic differences in clinical signs and symptoms.

OBJECTIVES: To determine whether Asian and white subjects differ in clinical signs or subjective symptoms in response to the use of different biguanide-preserved contact lens care solutions. METHODS: Forty-two subjects (15 Asian and 27 white) wearing lotrafilcon B silicone hydrogel contact lenses used a preservative-free lens care solution bilaterally for 2 weeks, then used two biguanide-preserved solutions (solution 1: ReNu MPS; solution 2: AQuify MPS) contralaterally in randomly assigned eyes for 4 weeks. Comprehensive ocular surface examinations were performed and symptomatology questionnaires were administered every 2 weeks. Investigators were masked as to solution assignment during examinations, whereas subjects were not to avoid potential difficulties in compliance with the protocol. RESULTS: With solution 1, most Asian and white subjects had grade 2 or greater corneal staining after 2 weeks (67% and 59%, respectively) and 4 weeks (60% and 67%, respectively). With solution 2, grade 2 or greater corneal staining occurred in 40% of Asians after 2 weeks and in 13% after 4 weeks, but in only 4% of whites after 2 weeks and 0% after 4 weeks. Whites reported significantly better average comfort (P=0.046) and less dryness (P<0.001) than did Asians. CONCLUSIONS: Asians and whites differ in both ocular response to the use of contact lens care solutions and in reporting subjective symptoms. Racial and ethnic differences should be considered when evaluating and treating contact lens patients in a clinical setting.

Clinical and pathological characteristics of ocular surface squamous neoplasia in an Asian population.

BACKGROUND: In order to evaluate clinical and pathological characteristics of ocular surface squamous neoplasia (OSSN) in Asian population. METHODS: Medical records were reviewed of 30 eyes of 30 Korean patients who underwent en-bloc excision and biopsy for tumors in the corneal and conjunctival epithelium in the suspicion of OSSN. RESULTS: Tumors developed predominantly in males (21/30 patients, 70%) at the mean age of 64.8 years (range: 39-82 years). Histologic examination revealed that 11 cases were squamous cell carcinoma (SCC), eight were conjunctival or corneal intraepithelial neoplasm (CIN) with dysplastic cells in the epithelium, eight simple hyperplasia, and three inflammatory lesions. The majority of SCC (9/11 eyes, 81.8%) involved the nasal conjunctiva and cornea, while one of eight eyes (12.5%) with CIN was located at the nasal side. Vascularization was combined in all eyes with SCC, in two of eight (25%) with CIN, in two of three with inflammation, and in none with hyperplasia. Both cornea and conjunctiva were involved in ten of 11 eyes (90.9%) with SCC, in six of eight (75%) with CIN, in two of eight (25%) with hyperplasia, and in two of three (66.7%) with inflammation. When classified based on clinical appearance, seven of 11 eyes (63.6%) with SCC were papilliform sessile masses, and four of eight (50 %) with CIN showed gelatinous growth onto the surface. All lesions were treated with en-bloc excision and cryotherapy. Recurrence occurred in seven out of 19 patients (36.8%) with SCC or CIN during the mean follow-up of 30.0 months-four patients with SCC and three with CIN. Hyperplasia or lesions with inflammation did not recur. The recurrence rate was not associated with histological diagnosis of a lesion. However, the use of the postoperative chemotherapy including topical mitomycin C or interferon α 2b had a significant negative correlation with the recurrence. CONCLUSIONS: In total, 36.7% of tumors in the corneal and conjunctival epithelium were SCC, and 26.7% were CIN. Recurrence occurred in 36.8% of patients with SCC or CIN after primary excision and cryotherapy. The use of postoperative chemotherapy was a significant factor negatively affecting the recurrence.

Genetic background and climatic droplet keratopathy incidence in a Mapuche population from Argentina.

PURPOSE: To determine whether the incidence of and susceptibility to climatic droplet keratopathy (CDK), an acquired, often bilateral degenerative corneal disease, is influenced by the genetic background of the individuals who exhibit the disorder. METHODS: To determine whether the disease expression was influenced by the genetic ancestry of CDK cases in native Mapuche of the northwest area of Patagonia in Argentina, we examined mitochondrial DNA and Y-chromosome variation in 53 unrelated individuals. Twenty-nine of them were part of the CDK (patient) population, while 24 were part of the control group. The analysis revealed the maternal and paternal lineages that were present in the two study groups. RESULTS: This analysis demonstrated that nearly all persons had a Native American mtDNA background, whereas 50% of the CDK group and 37% of the control group had Native American paternal ancestry, respectively. There was no significant difference in the frequencies of mtDNA haplogroups between the CDK patient and control groups. Although the Y-chromosome data revealed differences in specific haplogroup frequencies between these two groups, there was no statistically significant relationship between individual paternal genetic backgrounds and the incidence or stage of disease. CONCLUSIONS: These results indicate a lack of correlation between genetic ancestry as represented by haploid genetic systems and the incidence of CDK in Mapuche populations. In addition, the mtDNA appears to play less of a role in CDK expression than for other complex diseases linked to bioenergetic processes. However, further analysis of the mtDNA genome sequence and other genes involved in corneal function may reveal the more precise role that mitochondria play in the expression of CDK.

Association of variants in FRAP1 and PDGFRA with corneal curvature in Asian populations from Singapore.

Corneal curvature (CC) is a key determinant of major eye diseases, such as keratoconus, myopia and corneal astigmatism. No prior studies have discovered the genes for CC. Here we report the findings from four genome-wide association studies of CC in 10 008 samples from three population groups in Singapore. Our discovery phase surveyed 2867 Chinese and 3072 Malays, allowing us to identify two loci that were associated with CC variation: FRAP1 on chromosome 1p36.2 and PDGFRA on chromosome 4q12. These findings were subsequently replicated in a validation study involving an additional 2953 Asian Indians and a further collection of 1116 Chinese children. The effect sizes of the identified variants were consistent across all four cohorts, with seven single nucleotide polymorphisms (SNPs) in FRAP1 (lead SNP: rs17036350, meta P-value = 4.06 × 10(-13)) and six SNPs in PDGFRA (lead SNP: rs2114039, meta P-value = 1.33 × 10(-9)) attaining genome-wide significance in the SNP-based meta-analysis of the four studies. This is the first genome-wide survey of CC variation and we have identified two implicated loci in three genetically diverse Asian populations, suggesting the presence of common genetic etiology across multiple populations.

Refractive and corneal astigmatism in white school children in northern ireland.

PURPOSE: To study the prevalence of and relation between refractive and corneal astigmatism in white school children in Northern Ireland and to describe the association between refractive astigmatism and refractive error. METHODS: Stratified random clustering was used to recruit 1053 white children, 392 aged 6-7 years and 661 aged 12-13 years. Eye examinations included cycloplegic autorefraction and ocular biometric measures of axial length and corneal curvature. RESULTS: The prevalence of refractive astigmatism (≥ 1 DC) did not differ significantly between 6- to 7-year-old children (24%; 95% confidence interval [CI], 19-30) and 12- to 13-year-old children (20%; 95% CI, 14-25). The prevalence of corneal astigmatism (≥ 1 DC) also did not differ significantly between 6- to 7-year-old children (29%; 95% CI, 24-34) and 12- to 13-year-old children (25%; 95% CI, 21-28). While levels of refractive astigmatism and corneal astigmatism were similar, refractive astigmatism was predominantly oblique (76%; 95% CI, 67-85, of 6- to 7-year-olds; 59%; 95% CI, 48-70, of 12- to 13-year-olds), but corneal astigmatism was predominantly with-the-rule (80%; 95% CI, 72-87, of 6- to 7-year-olds; 82%; 95% CI, 74-90, of 12- to 13-year-olds). The prevalence of refractive astigmatism was associated with increasing myopia and hyperopia. CONCLUSIONS: This study is the first to provide robust population-based data on the prevalence of astigmatism in white school children in the United Kingdom. The prevalence of refractive astigmatism and corneal astigmatism is stable between 6 and 7 years and 12 and 13 years, although this finding would need to be confirmed by prospective studies. There is a high prevalence of refractive and corneal astigmatism which is associated with ametropia.

Epiblepharon in East asian patients: the singapore experience.

PURPOSE: To describe the demographics, presenting symptoms, indications for surgery, and surgical outcomes of epiblepharon correction in a tertiary care hospital in Singapore. DESIGN: Retrospective review of patients who underwent surgery by 2 surgeons in a referral oculoplastic practice at the National University Health System, Singapore, from 2001 to 2007. PARTICIPANTS: A total of 108 patients who underwent surgery for clinically significant epiblepharon. INTERVENTION: Modified Hotz procedure or suture correction for patients in whom conservative treatment failed. MAIN OUTCOME MEASURES: Comparison of symptoms, keratopathy, and recurrence on follow-up between the 2 procedures. RESULTS: The mean age of the patients was 9.0 years, with an age range of 0.5 to 68 years. Of the patients, 51.9% were male. The majority were Chinese (n = 102). Seventy-four (68.5%) patients were symptomatic. Eighty-nine patients (82.4%) had keratopathy. In 98 patients (90.7%) both eyes were affected, and the majority of patients (75.0%) had epiblepharon of the lower lids. Initial treatment for the majority was lubricants (n = 71, 65.7%). The main indications for surgery were symptoms and keratopathy, with 37.9% of patients having both, and 44.4% and 15.7% of patients having either keratopathy or symptoms alone, respectively. Surgical correction consisted mostly of a modified Hotz procedure (n = 88, 81.5%), lid-everting sutures (n = 9, 8.3%), and others, including upper lid blepharoplasty with lid crease formation (n = 11, 10.2%). Outcomes were good, with the majority (n = 88, 81.5%) of lids being well corrected. Complications included undercorrection, overcorrection, wound dehiscence, and wound infections. CONCLUSIONS: Symptomatic epiblepharon, usually associated with keratopathy and commonly seen in children of East Asian descent, often requires surgical intervention with good surgical outcome. Increased awareness among ophthalmologists and pediatricians dealing with this ethnic group and age is emphasized. Contrary to the current practice of expectant observation, definitive surgical management should be considered when symptoms or keratopathy is present. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Gundersen flaps in the management of ocular surface disease in an Asian population.

PURPOSE: To evaluate the indications, complications, and long-term outcomes with the use of a Gundersen flap for the treatment of various ocular surface conditions in an Asian population. DESIGN: Retrospective case series. STUDY SUBJECTS: Twenty-five eyes of 25 subjects who had undergone conjunctival flap surgery performed from 1999 to 2004 at the Singapore National Eye Centre. METHODS: Review of case records for indications and outcomes of patients undergoing Gundersen flap surgery. MAIN OUTCOME MEASURES: Surgical success was defined as attainment of a stable ocular surface with resolution of symptoms and no flap retraction or dehiscence resulting in reexposure of the corneal surface. Complications to be noted included infection, progression of the inflammatory or infectious disease process beneath the flap, flap loss from epithelial ingrowth, and epithelial cyst formation. RESULTS: Surgical success was achieved in all eyes. Intraoperative and postoperative complications were encountered in 6 patients (24%). One case had a buttonhole, 3 cases had partial flap retractions, and 2 had epithelial inclusion cysts. CONCLUSIONS: The Gundersen flap is still an important procedure and should be considered as a means of stabilizing globe integrity in the management of cases of severe ocular surface disease, particularly when visual potential is poor.

Mapping of a gene causing brittle cornea syndrome in Tunisian jews to 16q24.

PURPOSE: To map the gene that causes brittle cornea syndrome (BCS). METHODS: Five patients from four families, all of Jewish Tunisian origin, were recruited into the study. Four of the five patients had red hair. DNA from the five patients and 104 control chromosomes was typed with seven 16q polymorphic markers surrounding the hair color gene, MC1R. RESULTS: A common haplotype in the homozygous state, comprising five markers spanning 4.7 Mb on chromosome 16q24, was found in all five patients but in none of the control subjects (P < 0.00001). CONCLUSIONS: The gene that causes BCS maps to a 4.7-Mb interval, between the markers D16S3423 and D16S3425 on 16q24.

Navajo neurohepatopathy is caused by a mutation in the MPV17 gene.

Navajo neurohepatopathy (NNH) is an autosomal recessive disease that is prevalent among Navajo children in the southwestern United States. The major clinical features are hepatopathy, peripheral neuropathy, corneal anesthesia and scarring, acral mutilation, cerebral leukoencephalopathy, failure to thrive, and recurrent metabolic acidosis with intercurrent infections. Infantile, childhood, and classic forms of NNH have been described. Mitochondrial DNA (mtDNA) depletion was detected in the livers of two patients, suggesting a primary defect in mtDNA maintenance. Homozygosity mapping of two families with NNH suggested linkage to chromosome 2p24. This locus includes the MPV17 gene, which, when mutated, causes a hepatocerebral form of mtDNA depletion. Sequencing of the MPV17 gene in six patients with NNH from five families revealed the homozygous R50Q mutation described elsewhere. Identification of a single missense mutation in patients with NNH confirms that the disease is probably due to a founder effect and extends the phenotypic spectrum associated with MPV17 mutations.

Assessment of the anterior structures of eyes in a normal Northern Thai group using the Orbscan II.

OBJECTIVES: To evaluate the anterior structures of the eyes in normal Northern Thais include the corneal topography and thickness, as well as the anterior chamber depth (ACD) and the white-to-white (WTW) using the Orbscan II system. MATERIAL AND METHOD: One hundred and six eyes of 56 normal subjects were investigated using the Orbscan II. The simulated keratometry (SimK), astigmatism, corneal thickness, ACD and WTW were collected. The axial power maps as well as anterior and posterior elevation maps were read and categorized. Corneal thickness was measured in different regions and the pachymetry patterns were classified. RESULTS: The mean SimK was 44.18 (1.41)/43.30 (1.46) diopters (D) and the mean astigmatism was 0.93 (0.58) D. Symmetric bow tie was the most common axial power pattern in the anterior cornea (57.6%), followed by asymmetric bow tie (19.8%), irregular patterns (12.3%), round (9.4%), and oval (0.9%). Incomplete ridge (40.6%) and island (34%) were common elevation patterns observed in the anterior corneal surface, and island (92.5%) was the most common topographic pattern in the posterior. The thinnest point on the cornea had an average thickness of 512.49 (35) micron and was located at an average of 0.43 (0.24) mm from visual axis. In the pachymetry maps, round (47.2%) and oval (45.3%) were common patterns. The mean ACD and WTW was 2.79 (0.35) and 11.61 (0.36) mm, respectively. CONCLUSION: The present study demonstrated the normal variations of anterior segment structures of the eyes in normal Northern Thais using the Orbscan II topography system. This information may be useful for comparison with further quantitative studies of various abnormal states.