Demographic, clinical and tomographic characteristics of pellucid marginal degeneration patients in South Egyptian population.

PURPOSE: To retrospectively evaluate the demographic, clinical, and tomographic characteristics of pellucid marginal degeneration (PMD) patients in South Egypt. METHODS: This study was retrospective cross-sectional, including all patients who attended and sought refractive surgery at Sohag Center for Corneal and Refractive Surgeries, Sohag, South Egypt, between October 2016 and October 2020, and had a diagnosis of PMD. It included cases of PMD at different stages. Cases with PMD were diagnosed by the two authors (experienced in corneal refractive surgery), combining both slit-lamp biomicroscopy findings and corneal tomography. RESULTS: Out of the 2534 patients attending the Sohag Center for Corneal and Refractive Surgeries (between October 2016 and May 2020) seeking correction of their refractive errors, 24 patients were found to fit in the diagnosis of PMD. Forty-three eyes of the 24 patients were diagnosed with PMD. The topographic patterns ranged from horizontal bow tie (against the rule astigmatism) being the least presenting, followed by crab claw, then butterfly pattern. CONCLUSION: PMD is a separate entity of the ectatic corneal spectrum that can easily be misinterpreted as Keratoconus. Topographic and tomographic patterns cannot solely diagnose PMD as they should be enforced by slit-lamp findings.

Clinical profile and demographic distribution of pellucid marginal corneal degeneration in India: A study of 559 patients.

PURPOSE: The aim of this study was to describe the clinical profile and demographic distribution of pellucid marginal corneal degeneration (PMD) in patients presenting to a multitier ophthalmology hospital network in India. METHODS: This cross-sectional hospital-based study included 2,470,793 new patients presenting between September 2012 and September 2020 (~8 years period). Patients with a clinical diagnosis of PMD in at least one eye were included as cases. The data were collected using an electronic medical record system. RESULTS: Overall, 559 (0.02%) new patients were diagnosed with PMD. The prevalence rates were 0.004% in children (age <16 years) and 0.03% in adults. The majority of patients were males (70.13%) with the bilateral affliction (77.1%). The mean age of the patients was 37.91 ± 13.19 years. The majority (30.23%) of the patients were between 31 and 40 years of age. A significant number of patients were from higher socioeconomic status (93.74%) and from the urban region (45.08%). Of the 990 eyes, the most common clinical signs were ectasia/thinning (58.99%), corneal scar (17.47%), and corneal hydrops (1.01%). The majority of the eyes (87.97%) were managed with either spectacles or contact lenses. Among those who had surgical intervention, collagen cross-linking was the most performed procedure (5.25%) followed by cataract surgery (4.14%). CONCLUSION: PMD is a rare disease affecting patients seeking eye care in India. It commonly affects adult males and is bilateral in nature. The disease progression is slow and usually occurs beyond 3 years. Conservative management is more common than surgical intervention.

Clinical Profile and Demographic Distribution of Corneal Dystrophies in India: A Study of 4198 Patients.

PURPOSE: To describe the clinical profile and demographic distribution of corneal dystrophy in patients presenting to a multitier ophthalmology hospital network in India. METHODS: This cross-sectional hospital-based study included 2,151,584 new patients presenting between March 2012 and December 2019 (∼8 year period). Patients with a clinical diagnosis of corneal dystrophy in at least 1 eye were included as cases. The data were collected by using an electronic medical record system. RESULTS: Overall, 4198 new patients (0.20%) were diagnosed with corneal dystrophy. The prevalence rates were 0.19% in children (age < 16 years) and 0.20% in adults. Most patients were women (51.86%). The mean age of the patients was 43.61 ± 21.39 years. Most patients (18.79%) were between 61 and 70 years of age. The most common anatomical location of the dystrophy was endothelium (51.71%), followed by stroma (43.55%) and Bowman membrane/epithelium (4.73%). The most common corneal dystrophy was Fuch endothelial corneal dystrophy (41.89%). Most eyes had mild or no visual impairment (43.43%). Of the 8193 eyes, 998 eyes (12.18%) underwent a corneal surgery. Among those who underwent surgical intervention, endothelial keratoplasty was the most commonly performed surgical procedure (52%), followed by penetrating keratoplasty (22%). CONCLUSIONS: Corneal dystrophy is a rare disease, affecting patients seeking eye care in India. Endothelial dystrophies were the most common, followed by stromal dystrophies. Among the stromal dystrophies, macular dystrophy was the most common. At initial presentation, visual impairment was mild to moderate in most patients, and surgical intervention was needed in 12.18% of the eyes during the study period.

Changing Trends in Penetrating Keratoplasty Indications between 2011 and 2018 - Histopathology of 2123 Corneal Buttons in a Single Center in Germany.

Purpose: To analyse the changing trends in penetrating keratoplasty indications between January 2011 and December 2018, at the Department of Ophthalmology, Saarland University Medical Center, Homburg/Saar, Germany. Patients and Methods: This is a retrospective review of 2123 corneal buttons of 1776 patients (1993 eyes, 56.0% males, age at the time of surgery 57.6 ± 18.7 years), who underwent penetrating keratoplasty (PKP) between January 2011 and December 2018. The classification was performed based on histological analysis and using the priority scheme of Brady et al., supplemented by a group of "failed endothelial keratoplasty grafts". Our groups were the following: pseudophakic or aphakic bullous keratopathy, regraft, failed endothelial keratoplasty graft, acute necrotizing and ulcerative keratitis, keratoconus, Fuchs' dystrophy, corneal dystrophy other than Fuchs', corneal scars and other diagnoses. Results: Between 2011 and 2018, keratoconus was the leading indication for PKP in 455 (21.5%) cases, followed by acute necrotizing and ulcerative keratitis in 384 (18.1%), regraft in 367 (17.3%), corneal scars in 350 (16.5%), pseudophakic or aphakic bullous keratopathy in 225 (10.6%), Fuchs' dystrophy in 194 (9.1%), other diagnoses in 64 (3.0%), corneal dystrophy other than Fuchs' in 52 (2.4%), and failed endothelial keratoplasty graft in 32 (1.5%) cases. Conclusions: With the introduction of posterior lamellar keratoplasty, keratoconus remains the leading PKP indication in our center with excimer laser-trephination on a routine basis. A trend towards increasing numbers can be observed regarding acute necrotizing and ulcerative keratitis patients and regrafts. However, the incidence of Fuchs' dystrophy decreased dramatically within PKP patients, with the introduction of posterior lamellar keratoplasty.

Chorionic villus sampling: 10 years of experience in a University referral center.

OBJECTIVES: The purpose of this study was to estimate our center-specific CVS-related miscarriage rate. METHODS: This is an observational retrospective study of women submitted to a CVS in our hospital, between January 1st, 2007 and December 31st, 2016. Maternal and pregnancy characteristics, procedure details, genetic results and pregnancy outcomes of all patients were collected. The FMF miscarriage risk algorithm was used to estimate our population expected risk of miscarriage. To establish the procedure-related risk of miscarriage, we compared the observed with the expected miscarriage rate. RESULTS: We had a total number of 1523 women with a singleton pregnancy who did a CVS over the 10-year period. The mean maternal age was 34 years old; the majority of the women was Caucasian, multiparous and had a spontaneous pregnancy. The most common indication for CVS was a high-risk result in the 1st trimester combined screening test. The karyotype was normal in 72,7% of cases, 11,1% were T21 and 7,2% were T13 or T18. In the study group, 33 women were diagnosed with a fetal demise, 435 had a TOP and there were 4 intrauterine deaths and 34 miscarriages. The rate of miscarriage in our population was 3,2% and the expected patient specific risk for miscarriage was 3,0%. There was no statistical significance between the two miscarriage rates p = 0,705. CONCLUSION: In our study the risk of miscarriage in the CVS group was not significantly different from that the expected patient specific risk (3.2 % vs 3%, p = 0.7). The procedure-related risk of miscarriage was 0,2%, similar to the rates describe in the literature. An accurate risk of pregnancy loss should be used when counseling women for CVS to allow an informed decision.

Recurrent corneal erosion syndrome.

Recurrent corneal erosion syndrome (RCES) is a disorder characterised by a dysfunctional epithelial ecosystem. It often begins after trauma, or in the setting of epithelial basement membrane degeneration or dystrophy. Historically, RCES has been understood as a structural derangement of the anterior corneal architecture. More recently, studies have demonstrated the important role of neuropeptides in corneal homoeostasis. Thus, RCES may also be understood as a disorder of corneal epithelial cell biology. Management of RCES can be challenging, but newer therapies have demonstrated improved efficacy for this condition. This review examines the aetiology and pathogenesis of RCES, and provides an update on current and emerging treatment modalities for the management of this disorder.

Natural course of Finnish gelsolin amyloidosis.

BACKGROUND: Finnish type of hereditary gelsolin amyloidosis (FGA) is one of the most common diseases of Finnish disease heritage. Existing FGA knowledge is based only on smaller patient series, so our aim was to elucidate the natural course of the disease in a comprehensive sample of patients and to build up a national FGA patient registry. METHODS: An inquiry about the known and suspected signs of FGA, sent to the members of Finnish Amyloidosis Association, telephone contacts, and hospital records were utilized to create the registry. RESULTS: A total of 227 patients were entered to the database. The first symptom was ophthalmological for 167 patients (73.6%) at the mean age of 39 years. Corneal lattice dystrophy (CLD) was reported at the mean age of 43 years. Impaired vision, polyneuropathy, facial nerve paresis, and cutis laxa appeared on average between 52 and 57 years. Carpal tunnel syndrome (CTS) was reported by 86 patients (37.9%). Nine patients (4.0%) had a pacemaker, and 12 (6.1%) had cardiomyopathy. CONCLUSIONS: The first symptom was ophthalmological in most cases. Except for CLD no prominent difference in the age of appearance was found between the major symptoms. CTS, cardiac pacemakers, and cardiomyopathy were remarkably more common compared to the general population.

TGFBI, CHST6, and GSN gene analysis in Mexican patients with stromal corneal dystrophies.

OBJECTIVES: The purpose of our study was to describe the results of molecular screening of TGFBI, CHST6, and GSN genes in a group of Mexican patients with different stromal corneal dystrophies (CD). MATERIAL AND METHODS: A total of 16 CD Mexican patients pertaining to nine different pedigrees were subjected to a complete ophthalmological investigation. A clinical diagnosis of lattice CD was performed in 10 patients from five pedigrees. Three patients from two pedigrees were diagnosed with granular CD type 2, two patients with unrelated probands had Finnish-type corneal amyloidosis, and one patient had macular CD. Genetic analysis included DNA isolation from blood leukocytes and polymerase chain reaction (PCR) amplification and direct nucleotide sequencing of TGFBI, CHST6, and GSN genes. RESULTS: Seven lattice CD patients from four unrelated families had an identical p.H626R mutation in TGFBI, three patients from a single lattice CD family carried a p.R124C substitution in TGFBI, and a granular type 2 CD pedigree was demonstrated to carry a heterozygous TGFBI p.M619K substitution. A patient having Finnish-type corneal amyloidosis had a p.D187N mutation in GSN. Finally, molecular analysis of CHST6 in a patient with macular CD disclosed the presence of a homozygous p.Y110C change. CONCLUSIONS: This study improves the knowledge of the genetic features of Mexican patients with corneal stromal dystrophies by identifying mutations in the TGFBI, CHST6, and GSN genes. Genetic screening of larger samples of patients from distinct ethnic groups would be of great importance for a better understanding of the mutational spectrum of stromal CD.

Hereditary gelsolin amyloidosis.

Hereditary gelsolin amyloidosis (HGA) is an autosomally dominantly inherited form of systemic amyloidosis, characterized mainly by cranial and sensory peripheral neuropathy, corneal lattice dystrophy, and cutis laxa. HGA, originally reported from Finland and now increasingly from other countries in Europe, North and South America, and Asia, may still be underdiagnosed worldwide. It is the first and so-far only known disorder caused by a gelsolin gene defect, namely a G654A or G654T mutation. Gelsolin is a principal actin-modulating protein, implicated in multiple biological processes, also in the nervous system, e.g. axonal transport, myelination, neurite outgrowth, and neuroprotection. The gelsolin gene defect causes expression of variant gelsolin, followed by systemic deposition of gelsolin amyloid (AGel) in HGA patients and even other consequences on the metabolism and function of gelsolin. In HGA, specific therapy is not yet available but correct diagnosis enables adequate symptomatic treatment which decisively improves the quality of life in these patients. A transgenic murine model of HGA expressing AGel is available, in anticipation of new treatment options targeted toward this slowly progressive but devastating amyloidosis. Present and future lessons learned from HGA may be applicable even in diagnosis and treatment of other hereditary and sporadic amyloidoses.

Corneal stromal dystrophies: a clinical pathologic study / Distrofia corneana estromal: um estudo clínicopatológico

INTRODUCTION: Corneal dystrophy is defined as bilateral and symmetric primary corneal disease, without previous associated ocular inflammation. Corneal dystrophies are classified according to the involved corneal layer in superficial, stromal, and posterior dystrophy. Incidence of each dystrophy varies according to the geographic region studied. PURPOSE: To evaluate the prevalence of stromal corneal dystrophies among corneal buttons specimens obtained by penetrating keratoplasty (PK) in an ocular pathology laboratory and to correlate the diagnosis with patient age and gender. METHODS: Corneal button cases of penetrating keratoplasty from January-1996 to May-2009 were retrieved from the archives of The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, Montreal, Canada. The cases with histopathological diagnosis of stromal corneal dystrophies were stained with special stains (Peroxid acid Schiff, Masson trichrome, Congo red analyzed under polarized light, and alcian blue) for classification and correlated with epidemiological information (age at time of PK and gender) from patients' file. RESULTS: 1,300 corneal buttons cases with clinical diagnose of corneal dystrophy were retrieved. Stromal corneal dystrophy was found in 40 (3.1%) cases. Lattice corneal dystrophy was the most prevalent with 26 cases (65%). Nineteen were female (73.07%) and the PK was performed at average age of 59.3 years old. Combined corneal dystrophy was found in 8 (20%) cases, 5 (62.5%) of them were female and the average age of the penetrating keratoplasty was 54.8 years old. Granular corneal dystrophy was represented by 5 (12.5%) cases, and 2 (40%) of them were female. Penetrating keratoplasty was performed at average age of 39.5 years old in granular corneal dystrophy cases. Macular corneal dystrophy was present in only 1 (2.5%) case, in a 36 years old female. CONCLUSION: Systematic histopathological approach and evaluation, including special stains in all stromal corneal dystrophies is critical to establish the correct diagnosis.

INTRODUÇÃO: A distrofia corneana é definida como doença primária da córnea, bilateral e simétrica, sem associação com inflamação ocular prévia. Distrofias corneanas são classificados de acordo com a camada corneana envolvida em distrofia superficial, estromal e posterior. A incidência de cada distrofia varia de acordo com a região geográfica estudada. OBJETIVO: Avaliar a prevalência de distrofias corneanas estromal em botões corneanos de espécimes obtidos por ceratoplastia penetrante (CP), oriundos do arquivo de um laboratório de patologia ocular e correlacionar o diagnóstico com a idade e o sexo dos pacientes. MÉTODOS: Os botões corneanos oriundos de ceratoplastia penetrante recebidos entre janeiro de 1996 e maio de 2009 foram selecionados dos arquivos do Henry C. Witelson Ocular Pathology and Registry Laboratory, em Montreal, Canadá. Os casos com diagnóstico histopatológico de distrofias corneanas estromal foram corados com colorações especiais ("Peroxid acid Schiff", tricrômico de Masson, vermelho Congo analisadas sob luz polarizada, e "alcian blue") para a classificação e foram correlacionados com dados epidemiológicos (idade na época da ceratoplastia penetrante e sexo) dos pacientes. RESULTADOS: 1.300 casos de botões corneanos com diagnóstico clínico de distrofia corneana foram recuperados. Distrofia corneana estromal foi encontrada em 40 (3,1%) dos casos. Distrofia corneana lattice foi a mais prevalente com 26 casos (65%). Dezenove eram do sexo feminino (73,07%) e CP foi realizada em média com 59,3 anos de idade. Distrofia corneana combinada foi encontrada em 8 (20%) casos, 5 (62,5%) eram do sexo feminino e a idade média da CP foi de 54,8 anos. Distrofia corneana granular foi encontrada em 5 (12,5%) casos, e 2 (40%) deles eram do sexo feminino. A ceratoplastia penetrante foi realizada na média de idade de 39,5 anos, em casos de distrofia corneana granular. A distrofia corneana macular esteve presente em apenas um caso (2,5%), 36 anos de idade do sexo feminino. CONCLUSÃO: A abordagem histopatológica e avaliação sistemáticas, incluindo colorações especiais em todas as distrofias corneanas é essencial para estabelecer o correto diagnóstico.

TGFBI gene mutations in a Korean population with corneal dystrophy.

PURPOSE: To investigate the clinical and genetic features of Korean patients with corneal dystrophies associated with mutations in the human transforming growth factor-ß-induced (TGFBI) gene. METHODS: In this study, 387 subjects (71 families and 89 individuals - 268 patients having TGFBI corneal dystrophies and 119 normal relatives) were assessed. All subjects underwent a complete ophthalmologic evaluation, including biomicroscopic inspection and dilated fundus examination. As a control, 100 individuals without corneal disease were selected from the general population. The polymerase chain reaction (PCR) and direct sequencing were used to screen for mutations in TGFBI. RESULTS: All subjects recruited exhibited a range of corneal dystrophies, including Thiel-Behnke corneal dystrophy (TBCD, R555Q; 6 families and 4 individuals), granular corneal dystrophy type 2 (GCD2, R124H; 61 families and 80 individuals), lattice corneal dystrophy (LCD; 4 families and 5 individuals; 7 with type 1 [R124C], and 2 with a variant [L527R, P542R]). The disease showed an autosomal dominant inheritance pattern in all families. CONCLUSIONS: R124H in GCD2 was the most common mutation. GCD1 and Reis-Bucklers corneal dystrophy were not found. In the GCD2 patients there were a large number of laser refractive surgery-induced corneal opacities. A spontaneous R124H mutation was confirmed in an already mutated allele that resulted in a change from a heterozygous into a homozygous form. Also, a novel mutation, P527R, was identified in LCD.

Clinical and basic aspects of gelatinous drop-like corneal dystrophy.

Gelatinous drop-like corneal dystrophy (GDLD) was first reported in 1914 as a peculiar corneal dystrophy with an autosomal recessive inheritance mode. GDLD is rare in many countries, but relatively prevalent in Japan. The typical finding of GDLD is grayish, mulberry-like, protruding subepithelial depositions with a prominent hyperfluorescence of the cornea. Histologically, GDLD corneas are characterized by subepithelial amyloid depositions that were identified as lactoferrin by amino acid sequencing analysis. In 1998, the TACSTD2 gene was identified as a causative gene for this disease through a linkage analysis and a candidate gene approach. To date, 14 reports have demonstrated 21 mutations comprised of 9 missense, 6 nonsense, and 6 frameshift mutations from 9 ethnic back grounds. Currently, it is hypothesized that the loss of TACSTD2 gene function causes decreased epithelial barrier function, thereby facilitating tear fluid permeation into corneal tissue, the permeated lactoferrin then transforming into amyloid depositions via an unknown mechanism. For the visual rehabilitation of patients with GDLD, ophthalmologists currently employ various types of keratoplasties; however, almost all patients will experience a recurrence of the disease within a few years after such interventions. Wearing of a soft contact lens is sometimes considered as an alternative treatment for GDLD.

Salzmann's nodular corneal degeneration (SNCD): clinical findings, risk factors, prognosis and the role of previous contact lens wear.

PURPOSE: To revisit the clinical presentations of Salzmann's nodular corneal degeneration (SNCD) and to identify risk factors, occurrence and prognosis, and in particular to assess the role of previous contact lens wear as an aetiological factor. METHODS: Retrospective case note review of all cases of Salzmann's nodular degeneration over the last twenty years. We analysed epidemiological features, characteristics of lesions, risk factors and final outcomes. RESULTS: Thirty eyes (19 patients) were identified with SCND. Eleven patients had bilateral disease. Our cohort included 14 female (73.7%) and 5 males (26.3%). Average age at presentation was 58.9 (range 30-75) years. Follow up range was 0-13 years. The most common presenting symptom was foreign body sensation (68.4%). Ocular pathologies were: dry eyes (56%), chronic blepharitis (32%), trichiasis (8%), trachoma (32%), previous ocular trauma (8%), and previous ocular surgery (21.4%). Sixteen percent of cases were soft monthly disposable contact lens wearers. None of our patients with rigid contact lens wear developed Salzmann's nodules. Surgical excision was needed in 4 cases (13.3%). Two of them developed recurrent disease. CONCLUSION: Salzmann's nodular corneal degeneration is a disorder affecting middle-aged white women predominantly, and seems to be associated with concomitant chronic MGD, dry ocular surface, soft contact lens wear and previous ocular surgery. The prognosis is very good, and most patients are "successfully" treated with medical management alone, and therefore correct diagnosis of the disease is paramount. If indicated, various surgical options are available and give good outcomes. However, Salzmann's nodules can recur after penetrating keratoplasty.

Visual morbidity in thirty-four families with Schnyder crystalline corneal dystrophy (an American Ophthalmological Society thesis).

PURPOSE: To assess the findings, visual morbidity, and surgical intervention in Schnyder crystalline corneal dystrophy (SCCD). METHODS: Retrospective case series of 115 affected individuals from 34 SCCD families identified since 1989. Age, uncorrected visual acuity, best-corrected visual acuity (BCVA), corneal findings, and ocular surgery were recorded. Prospective phone, e-mail, or written contact provided updated information. Patients were divided into 3 age categories for statistical analysis: less than 26 years of age, 26 to 39 years of age, and 40 years of age and older. RESULTS: Mean age on initial examination was 38.8 +/- 20.4 (range, 2-81) with follow-up of 55 of 79 (70%) of American patients. While there were no statistical significant correlations between logMAR visual acuity and age (logMAR BCVA =.033 + .002 x age; R =.21), the linear regression showed the trend of worse visual acuity with age. BCVA at > or =40 years was decreased compared to <40 (P < .0001), although mean BCVA was > 20/30 in both groups. Twenty-nine of 115 patients had corneal surgery with 5 phototherapeutic keratectomy (3 patients), and 39 penetrating keratoplasty (PKP) (27 patients). PKP was reported in 20 of 37 (54%) patients > or =50 years and 10 of 13 (77%) of patients > or =70. BCVA 1 year prior to PKP in 15 eyes (9 patients) ranged from 20/25 to 20/400 including 7 eyes with other ocular pathology. BCVA in the remaining 8 eyes was 20/25 to 20/70 with 3 of these 4 patients reporting preoperative glare. Chart and phone survey suggested increasing difficulty with photopic vision with aging. CONCLUSION: Although excellent scotopic vision continues until middle age in SCCD, most patients had PKP by the 7th decade. SCCD causes progressive corneal opacification, which may result in glare and disproportionate loss of photopic vision.

[Geographical feature of lattice corneal dystrophy patients in Aichi Prefecture: an analysis of the TGFBI gene].

PURPOSE: To investigate the genetics of patients with lattice corneal dystrophy (LCD) in Aichi Prefecture, the majority of whom originated from the same area of Hazu-gun. METHODS: We studied twenty patients who visited Nagoya University Hospital from April 1997 to March 2000 and were diagnosed as having LCD. A complete history including a detailed family history was obtained from each of the patients. DNA analysis was performed on each patient with an informed consent. RESULTS: Fourteen patients had an obvious family history, and 7 pedigrees were detected. Four of the 7 families were from Hazu-gun, and Arg 124 Cys mutation in the TGF-beta indused gene human 3(TGFBI) gene was detected in the families. A family from Nishikasugai-gun had a Leu 518 Pro mutation in the same gene. Six patients were considered sporadic without any family history. However, a heterozygous single base-pair transition (leucine to arginine) was detected in codon 527 of the TGFBI gene in 4 out of these 6 patients. CONCLUSION: Genetic analysis confirmed that LCD observed in patients from Hazu-gun is a type I LCD caused by an Arg 124 Cys mutation in the TGFBI gene. TGFBI gene mutations, other than the Arg 124 Cys, were detected in a family with LCD type I in Aichi Prefecture. Among the autosomal dominant inherited LCDs, there is at times a sporadic pattern because of its late-onset form.

Association of autosomal dominantly inherited corneal dystrophies with BIGH3 gene mutations in Japan.

PURPOSE: To evaluate the incidence of BIGH3 gene mutations in 164 unrelated Japanese patients with corneal stromal dystrophies with an autosomal dominant trait. METHODS: Data were collected at two major institutions in the eastern and western parts of Japan, where molecular genetic analysis was performed for diagnostic purpose. RESULTS: The incidence of mutations was ranked as follows: 118 patients (72%), the R124H mutation associated with Avellino corneal dystrophy; 23 patients (14%), the R124C mutation associated with lattice corneal dystrophy type 1; and 10 patients (6%), the P501T mutation associated with lattice corneal dystrophy type 3A. CONCLUSION: Avellino corneal dystrophy associated with the R124H mutation is the most common form of corneal stromal dystrophy in Japan. This dystrophy, which is diagnosed histopathologically, has also been called granular corneal dystrophy in Japan. The classification of these diseases according to genetic pathogenesis may be more appropriate than is the use of clinical or histological findings.

The 2588G-->C mutation in the ABCR gene is a mild frequent founder mutation in the Western European population and allows the classification of ABCR mutations in patients with Stargardt disease.

In 40 western European patients with Stargardt disease (STGD), we found 19 novel mutations in the retina-specific ATP-binding cassette transporter (ABCR) gene, illustrating STGD's high allelic heterogeneity. One mutation, 2588G-->C, identified in 15 (37.5%) patients, shows linkage disequilibrium with a rare polymorphism (2828G-->A) in exon 19, suggesting a founder effect. The guanine at position 2588 is part of the 3' splice site of exon 17. Analysis of the lymphoblastoid cell mRNA of two STGD patients with the 2588G-->C mutation shows that the resulting mutant ABCR proteins either lack Gly863 or contain the missense mutation Gly863Ala. We hypothesize that the 2588G-->C alteration is a mild mutation that causes STGD only in combination with a severe ABCR mutation. This is supported in that the accompanying ABCR mutations in at least five of eight STGD patients are null (severe) and that a combination of two mild mutations has not been observed among 68 STGD patients. The 2588G-->C mutation is present in 1 of every 35 western Europeans, a rate higher than that of the most frequent severe autosomal recessive mutation, the cystic fibrosis conductance regulator gene mutation DeltaPhe508. Given an STGD incidence of 1/10,000, homozygosity for the 2588G-->C mutation or compound heterozygosity for this and other mild ABCR mutations probably does not result in an STGD phenotype.

Macular corneal dystrophy in Iceland. A clinical, genealogic, and immunohistochemical study of 28 patients.

BACKGROUND: The frequency of different types of macular corneal dystrophy (MCD) was determined in Iceland where MCD accounts for one third of every penetrating keratoplasty. METHODS: The authors determined the serum levels of antigenic keratan sulfate (aKS) in 27 patients with MCD and 53 unaffected family members by an enzyme-linked immunosorbent assay that uses an anti-KS monoclonal antibody (5-D-4). The authors also stained sections from 37 corneal buttons (including 2 regrafts) from 23 patients with MCD by the avidin-biotin complex method using the same anti-KS monoclonal antibody. RESULTS: Based on the serum analyses, 22 patients had MCD type I and 5 had MCD type II. The corneas from patients without detectable KS in the serum lacked immunohistochemical reactivity to the anti-KS antibody. Every MCD cornea examined from individuals with normal serum KS levels showed KS reactivity. All 53 unaffected siblings and parents carrying the recessive gene had normal serum KS levels. CONCLUSIONS: Macular corneal dystrophy types I (78.6%) and II (21.4%) both occur in Iceland. Members of affected sibships had only one of these types, not both. Nine patients with MCD type I and four persons with MCD type II belonged to a large pedigree in which individuals have been traced as far back as the beginning of the 16th century. The linking of patients with MCD types I and II in an inbred pedigree suggests that both types may be manifestations of the same abnormal gene rather than independent entities. The serum KS levels were not helpful in detecting heterozygous MCD carriers.

Contribuiçäo ao estudo das distrofias corneanas / Contribution to the study of corneal dystrophies

Foram analisados os prontuários e as córneas provenientes de 49 pacientes submetidos à ceratoplastia penetrante, com diagnóstico de distrofia, durante o período de 1982 a 1988. Destes casos, 16 pacientes (32,7%) eram do sexo masculino e 33 (67,3%) do sexo feminino. A idade média dos pacientes foi de 32 anos, variando de 7 a 76 anos. Entre as mulheres, a faixa etária compreendida entre 21 e 30 anos foi a que apresentou o maior número de casos. Em ordem decrescente as distrofias mais frequentes foram: Granular, Macular, Lattice, Fuchs, Reis-Buklers e Polimorfa Posterior

Recurrent erosion of the cornea.

Altogether, 80 patients aged between 24 and 73 years with recurrent erosion of the cornea have been studied and compared with a control group of 200. The patients' erosions were divisible into macroform and microform types. The macroform occurred in 10%, the microform in 56%, and both types in the same patients in 31%. The macroform was more commonly related to trauma than the microform. However, many (40%) were spontaneous in origin. The most common cause of the initial trauma was a finger nail. The recurrences occurred at around the time of waking, either just before or just after. Difficulty in opening the eye occurred in 10%. There was little evidence of precipitating factors, but eye rubbing was admitted by 10% and barbiturates were implicated in 3%. The corneae were examined in the healed state, when a high incidence (59%) were found to have superficial corneal dystrophies of the fingerprint lines, bleb, and Bietti's lacunar (map-like) types. These are considered individually, particular attention being paid to the distinction between the various types of line resembling the fingerprint line. Epithelial microcysts were also a common finding (59%) and were sometimes of the Cogan type. In only 11% of patients were there no corneal signs in the healed state. The need for careful examination of the cornea by retroillumination, using both the iris and the fundus, is stressed. The control group, in contrast, showed a very low incidence of dystrophies and cysts. Treatment was given initially with either drops or ointment and no differences in healing were found. Debridement was performed in 12 eyes as an initial treatment and also in four eyes which were not healing on medical treatment. Debridement assisted healing, but did not prevent recurrence. One eye was treated with debridement and scarification and seven with carbolization. These procedures appeared to reduce the recurrence rate. Sodium chloride ointment 5% was found useful as a prophylactic taken at bedtime, and the recurrence rate increased when it was withdrawn.