Lenticular Opacities Research Articles

Multiple transfused thalassemia major: Ocular manifestations in a hospital-based population

Purpose:To study the ocular manifestations in multiple transfused beta-thalassemia major patients and assess the ocular side-effects of iron chelating agents.Materials and Methods:In this prospective observational study, 45 multiple transfused beta-thalassemia major children between six months and 21 years of age were enrolled and assigned groups according to the treatment regimens suggested. Group A received only blood transfusions, Group B blood transfusions with subcutaneous desferrioxamine, Group C blood transfusions with desferrioxamine and oral deferriprone and Group D blood transfusions with deferriprone. Ocular status at the time of enrolment was documented. Subjects were observed quarterly for one year for changes in ocular status arising due to the disease process and due to iron chelation therapy. Children with hemoglobinopathies other than beta-thalassemia major, congenital ocular anomalies and anemia due to other causes were excluded.Results:Ocular involvement was observed in 58% of patients. Lenticular opacities were the most common ocular finding (44%), followed by decreased visual acuity (33%). An increased occurrence of ocular changes was observed with increase of serum ferritin and serum iron levels as well as with higher number of blood transfusions received. Desferrioxamine seemed to have a protective influence on retinal pigment epithelium (RPE) mottling. Occurrence of lenticular opacities and RPE degeneration correlated positively with use of desferrioxamine and deferriprone respectively. Follow-up of patients for one year did not reveal any change in ocular status.Conclusion:Regular ocular examinations can aid in preventing, delaying or ameliorating the ocular complications of thalassemia.

Исследование влияния дополнительного введения биотина на развитие помутнений в хрусталиках при моделировании световой катаракты

Исследование влияния дополнительного введения биотина на развитие помутнений в хрусталиках при моделировании световой катаракты

Correlation between cyanide-induced decreases in ocular Ca<sup>2+</sup>-ATPase and lenticular opacification

The effect of cyanide toxicity on Ca 2+ -ATPase activities were significantly decreased in the lens and vitreous humour of the cyanide-fed rabbits (p Keywords : Cyanide, Ca 2+ -ATPase, cataracts Journal of Medicine and Biomedical Research Vol. 3 (1) 2004: pp. 37-41

Alterações na tela de Amsler entre pacientes com catarata senil

PURPOSE: To assess the influence of some forms of lenticular opacification in the Amsler grid test among patients suffering from senile cataract. METHODS: Randomized, prospective interventional trial. Two hundred patients with senile cataract were evaluated with Amsler grid, measurement of best corrected visual acuity for near distance and far distance, biomicroscopy of the anterior segment and macular region. RESULTS: With a two months minimum of follow-up, the average visual acuity after surgery for far distance among the 200 patients was [...]

Subjective and quantitative measurement of wavefront aberrations in nuclear cataracts - a retrospective case controlled study

Purpose:To measure, quantify and compare Ocular Aberrations due to nuclear cataracts.Setting:Department of ophthalmology and school for ophthalmic technicians, college of medicine and health sciences, Sultan Qaboos University, Muscat, Oman.Design:Retrospective case controlled study.Methods:113 eyes of 77 patients with nuclear cataract (NC) were recruited from outpatient clinic of a major tertiary referral center for Ophthalmology. Patients having NC with no co-existing ocular pathologies were selected. All patients were subjected to wavefront aberrometry (make) using Hartmann-Shack (HS) aberrometer. Consents were taken from all patients. Higher order Aberrations (HOA) were calculated with Zernike polynomials up to the fourth order. For comparison 28 eyes of 15 subjects with no lenticular opacities (control group) were recruited and evaluated in an identical manner. No pupillary mydriasis was done in both groups.Results:Total aberrations were almost six times higher in NC group compared to control (normal) subjects. The HOA were 21 times higher in NC group, and coma was significantly higher in NC eyes compared to normal (control) group. The pupillary diameter was significantly larger in control group (5.48mm ± 1.0024, p<.001) compared to NC (3.05mm ± 1.9145) subjects (probably due to younger control age group). Amongst Zernike coefficients up to fourth order, two polynomials, defocus (Z20) and spherical aberration (Z42) were found to be significantly greater amongst NC group, compared to normal control group.Conclusion:Nuclear cataracts predominantly produce increased defocus and spherical aberrations. This could explain visual symptoms like image deterioration in spite of normal Visual acuity.

Fabry Disease

Fabry disease is a rare inherited lysosomal storage disorder caused by the partial or complete deficiency of the lysosomal enzyme alpha galactosidase A (alpha-Gal A), resulting in excess cellular glycosphingolipid deposition. Accumulation of the neutral glycosphingolipid globotriaosyl-ceramide predominates and involves small blood vessels, nerves, dorsal root ganglia, renal glomerular, and tubular epithelial cells and cardiomyocytes. Disease transmission is X-linked, therefore it predominantly affects males and females as asymptomatic carriers. However, females may also develop symptomatic disease of varying severity. Glycosphingolipid deposition in various tissues leads to episodic pain crises and acroparesthesias, gastrointestinal disturbances, angiokeratomas, corneal, and lenticular opacities, and eventually in the third to fifth decades of life, the kidney, heart and central nervous system are involved. Cardiac involvement is usually part of the multisystem disorder and presents in the fourth decade with other organ manifestations; however, a variant of Fabry disease with predominant cardiac manifestations has also been recognized. Patients may present with angina pectoris, dyspnea, palpitations, or syncope, and these symptoms are due to vascular, endothelial, myocardial (with increase in left ventricular mass), and conduction system involvement. Advanced cardiac disease may require a permanent pacemaker and cardiac transplant. Substrate inhibition with enzyme replacement therapy and gene therapy instituted early in the disease course might slow progression of the cardiac manifestations.

Transscleral IOL Fixation With Preserved Anterior Vitreous Face in Marfan Syndrome With Ectopia Lentis

Purpose: To evaluate the safety and efficacy of transscleral intraocular lens (IOL) fixation while preserving the anterior vitreous face in treating ectopia lentis of Marfan syndrome. Methods: This study included six patients (12 eyes) who had undergone surgical intervention for ectopia lentis with or without lenticular opacity. We compared the best-corrected visual acuity (BCVA) before and after the surgery and evaluated perioperative complications. Results: The mean age at the time of surgery was 18.210.7 years. The mean follow-up period was 11.27.1 months. Mean BCVA scores changed from 0.960.37 (LogMar Value) to 0.140.17 (LogMar Value). All patients showed more than two lines of improvement in visual acuity. In two eyes, pupillary capture was found. Medically controllable intraocular pressure elevation was found in three eyes. Conclusions: This study suggests that transscleral IOL fixation with a preserved anterior vitreous face can be a safe and effective technique in treating the ectopia lentis of Marfan syndrome.

The effect of acetyl-l-carnitine on lenticular calpain activity in prevention of selenite-induced cataractogenesis

The present study sought to determine whether acetyl-L-carnitine (ALCAR) prevents selenite cataractogenesis by mechanisms involving lenticular calpain activity, Wistar rat pups were divided into 3 groups of 15 each. Group I (normal) rats received an intraperitoneal (i.p.) injection of normal saline on postpartum day 10; Group II (cataract-untreated) rats received a single subcutaneous (s.c.) injection of sodium selenite (19micromol/kg body weight) on postpartum day 10; Group III (cataract-treated) pups received a single s.c. injection of sodium selenite on postpartum day 10 and intraperitoneal injections of acetyl-L-carnitine (200mg/kg body weight) on postpartum days 9-14. At the end of the study period (postpartum day 16), both eyes of each rat pup were examined by slit-lamp biomicroscopy. There was dense lenticular opacification in all Group II rats, minimal lenticular opacification in 33% of Group III rats, and no lenticular opacification in 67% of Group III and in all Group I rats. Group II lenses exhibited significantly lower mean values of calpain activity and Lp82 (lens-specific calpain) protein expression, decreases in relative transcript level of m-calpain mRNA and significantly higher mean Ca(2+) concentrations than Group I or Group III lenses; the values of these parameters in Group III rat lenses (ALCAR-treated) approximated those in Group I rat lenses. The results suggest that, in addition to its already-described antioxidant potential, ALCAR prevents selenite cataractogenesis by maintaining calpain activity at near normal levels. These findings may stimulate further efforts to develop ALCAR as a novel drug for prevention of cataract.

Switching from Deferoxamine (Desferal®, DFO) to Deferasirox (Exjade®) Maintains Effective Control of Iron Levels in Patients with Thalassemia Major (TM)

Background: The clinical outcome of transfusion-dependent TM patients with iron overload has been shown to depend on the dose and frequency of deferoxamine (DFO) use. However, the demanding regimen of slow subcutaneous infusions often leads to poor compliance. Deferasirox (Exjade®), a once-daily oral chelator, has potential compliance advantages. Doses of 20–30 mg/kg/day are non-inferior to DFO >35 mg/kg in TM patients with baseline liver iron concentration (LIC) >7 mg Fe/g dry weight (dw). This analysis reports efficacy and safety data from TM patients with iron overload who received DFO in a 1-year core trial (107), and then switched to deferasirox in an ongoing 4-year extension trial (107E).Methods: TM patients with iron overload ≥2 years of age were randomized to DFO or deferasirox in study 107. Patients with LIC <7 or ≥7 mg Fe/g dw received DFO <25–<35 or 35-≥50 mg/kg, respectively, but some patients with baseline LIC <7 mg Fe/g dw remained on their higher pre-study DFO doses since these were efficacious. Patients completing the 1-year core trial had a repeat LIC assessment by biopsy or SQUID, and were continued on or switched to deferasirox during 107E for long term efficacy and safety evaluation. Deferasirox dose was based on the end of 1-year LIC, and adjusted according to trends in serum ferritin (SF) level. Efficacy and safety data were analyzed annually for patients receiving DFO in study 107 who switched to deferasirox in 107E, to determine long-term outcome.Results: 259 patients, 129 children (2–<16 years) and 130 adults (≥16 years) are included. Average daily DFO dose during study 107 was 42.7±9.2 mg/kg; mean transfusional iron intake was 0.4±0.3 mg/kg/day (range 0.2–0.9). Baseline LIC was ≤7 and >7 mg Fe/g dw in 85 and 174 patients, respectively. Median SF change after 12 months of DFO was −264 ng/mL (baseline 2037 ng/mL). Patients crossed over to deferasirox and have received treatment for a median of 35.2 months. At month 42 of deferasirox, median SF had further decreased by −257 ng/mL (baseline 1843 ng/mL) in a dose-related manner (Figure 1). [Display omitted] During DFO treatment the most common drug-related AEs were injection-site reaction (n=6, 2.3%) and pain (n=6, 2.3%); no drug-related AEs led to discontinuation. One patient had a serious drug-related AE. Three patients (1.2%) had an alanine aminotransferase (ALT) increase >10 × ULN on at least one visit, where baseline ALT values were normal, ≥1–<5 × ULN and ≥5–<10 × ULN. Irrespective of relationship to DFO, deafness, tinnitus and hypoacusis were reported in five, four and three patients, while five and one had lenticular opacities and maculopathy, respectively.During year 1 of deferasirox treatment the most common drug-related AEs were rash (n=17, 6.6%), diarrhea (n=11, 4.2%) and nausea (n=7, 2.7%); the annual frequency of these drug-related AEs decreased to <1.5% thereafter. Five drug-related AEs led to discontinuation. Seven patients (2.7%) had a serious drug-related AE. In year 1, three patients (1.2%) had serum creatinine increases >33% above baseline and ULN on two consecutive visits, with a subsequent overall annual incidence of 2–3%. In year 1, four patients (1.5%) had an ALT increase >10×ULN on at least one visit (baseline values were ≥1–<5×ULN for three patients and ≥5–<10×ULN for the other), as did six patients in year 2 of deferasirox therapy; no ALT values >10×ULN were reported thereafter. Irrespective of relationship to deferasirox, hypoacusis, deafness and tinnitus were seen in four, two and one patients, respectively, and one had lenticular opacities.Conclusions: TM patients who have previously received chelation therapy with DFO can maintain effective chelation when switched to deferasirox, as demonstrated by a continued and dose-dependent decrease in SF. Over long-term deferasirox treatment with increased dose, there was no increased risk of toxicity, no evidence of progressive renal or liver dysfunction and an annual decrease in drug-related AEs.

Bilateral Metabolic Cataracts in 10-yr-old boy with newly diagnosed Type 1 Diabetes Mellitus

Classic symptoms of diabetes mellitus in childhood prompting parents to seek medical attention include polydipsia, polyuria, polyphagia, weight loss and kussmal breathing. Cataracts with juvenile diabetes usually occur in patients with long-standing, poorly controlled diabetes (1, 2). We describe a child in whom the acute loss of vision secondary to lenticular opacities was the initial sign of insulin-dependent diabetes mellitus.

Aggregation of crystallins induced by pulsed laser UV light (308 nm)

Here we compile and analyze the data on photoaggregation of a model protein carboanhydrase and the main eye lens proteins α-, β-, γ-crystallins under the action of pulsed UV irradiation from a Xe-Cl laser (308 nm) with broad variation of pulse energy density and repetition rate. The aggregation efficacy proves to be a nonlinear function of these parameters and protein concentration. A theoretical model is proposed that qualitatively explains the experimental data. It is shown that N-arm-truncated βA3-crystallin is more prone to UV-induced aggregation than the full-sized protein; such defects caused by mutation or aging may aggravate the development of lenticular opacity. Analyzed is the effect of some low-molecular compounds on the aggregation of β-crystallin and its mixture with α-crystallin. A combination of short peptides prepared on this basis markedly impedes crystallin aggregation and retards the development of UV-induced cataract in rats.

Visual acuity measurement and ocular co-morbidity in diabetic retinopathy screening

Aims:To evaluate the relationship between best corrected visual acuity (BCVA), age, type of diabetes, sight-threatening diabetic retinopathy (STDR) and ocular co-morbidity.Methods:1549 randomly selected people with diabetes mellitus (DM) from a...

Clinical findings following Ahmed Glaucoma Valve&amp;trade; implantation in pediatric glaucoma

To describe clinical findings after Ahmed valve drainage implantation in children. All records in one practice were reviewed to identify and describe clinical findings in all children who had undergone Ahmed Glaucoma Valve S2 model insertion for uncontrolled primary or secondary glaucoma. A total of 6 patients were identified, ranging in age from 2-15 years. Mean follow-up time averaged from 2-5 years from the time of tube insertion. Three patients exhibited pupillary peaking towards the tube of the valve. All patients required additional surgery or additional medications to control intraocular pressure. Lenticular opacification near the tube site developed in one patient. Gradual tube extrusion was also noted in another two patients. Multiple clinical events follow the Ahmed valve insertion in children. Pupillary irregularity is the most commonly noted event in this series. To avoid or reduce the risk of this complication, additional or modification of surgical procedures could be considered. The mechanism of such occurrence will further be discussed.

Noninvasive Measurement of Protein Aggregation by Mutant Huntingtin Fragments or α-Synuclein in the Lens

Many diverse human diseases are associated with protein aggregation in ordered fibrillar structures called amyloid. Amyloid formation may mediate aberrant protein interactions that culminate in neurodegeneration in Alzheimer, Huntington, and Parkinson diseases and in prion encephalopathies. Studies of protein aggregation in the brain are hampered by limitations in imaging techniques and often require invasive methods that can only be performed postmortem. Here we describe transgenic mice in which aggregation-prone proteins that cause Huntington and Parkinson disease are expressed in the ocular lens. Expression of a mutant huntingtin fragment or alpha-synuclein in the lens leads to protein aggregation and cataract formation, which can be monitored in real time by noninvasive, highly sensitive optical techniques. Expression of a mutant huntingtin fragment in mice lacking the major lens chaperone, alphaB-crystallin, markedly accelerated the onset and severity of aggregation, demonstrating that the endogenous chaperone activity of alphaB-crystallin suppresses aggregation in vivo. These novel mouse models will facilitate the characterization of protein aggregation in vivo and are being used in efficient and economical screens for chemical and genetic modifiers of disease-relevant protein aggregation.

Effect of methanolic extract of Allium sativum (AS) in delaying cataract in STZ-induced diabetic rats

Glycemic-induced stress is a major culprit contributing to oxidative insult that has far-reaching effects in diabetic cataract worldwide. In an attempt to prevent/delay cataract, many therapeutic agents have been identified, and among these, natural dietary sources have gained pharmacological significance. Hence, we investigated the efficacy of the methanolic garlic extract against diabetic cataract in Wistar rats. Methanolic garlic extract scavenged the transition metal ion-generated H(2)O(2) with an IC(50) of 768.8 +/- 1.76 mug/ml, showing its potential ability as an antioxidant. We have noticed lenticular opacity and oxidative damage in streptozotocin (STZ)-induced hyperglycemic rats. This is evident by the elevation of Ca(2+), Cu(2+), Na(+), Mg(2+), thiobarbituric acid reacting substances (TBARS), and carbonyl content and increased activities of polyol enzymes, glutathione peroxidase (GPx), superoxide dismutase (SOD), and up regulation of iNOS transcript and protein aggregation/cross-linking followed by a decrease in reduced glutathione (GSH), K(+) content, and tryptophan fluorescence in the cataractous lenses of STZ-induced diabetic rats. Garlic administration in a dose-dependent manner attenuated the glycemia-mediated oxidative stress as all the parameters have been found normalized more or less to that of control rats and thus delaying the progression of the lens opacity. We conclude that garlic extract has hypoglycemic and anti oxidant properties that can delay the progression of cataract as revealed in this study.

Effect of Laser Spot Diameter on the Reproducibility of Visual Field Analysis in Diabetic Patients with Upper Temporal Retinal Vein Occlusion

Aim: To evaluate the effect of the laser spot diameter on the reproducibility of the visual field analysis in diabetic patients with upper temporal retinal vein occlusion. Material and Methods: Thirty-six eyes of 36 consecutive type-2 diabetes mellitus patients with upper temporal retinal vein occlusion who required sectoral retinal photocoagulation (SRP) treatment were enrolled for the study. Patients with a history of previous retinal laser photocoagulation, significant lenticular opacities and those whose perimetric test reliability criteria were low (fixation loss >20% and false-positive or false-negative responses >33%) were excluded from the study. SRP was applied to the upper temporal retinal quadrant. Nineteen eyes received SRP treatment with 500-µm laser spots (group 1) while the rest of the eyes (n = 17) received SRP with 300-µm laser spots (group 2). Patients underwent five consecutive visual field analyses, each on a different day during a 2-week period, both before and 6 weeks after SRP. The Humphrey field analyzer central 30–2 threshold test using SITA Standard strategy was applied for visual field testing. Results: The mean age of the patients in groups 1 and 2 were 58.6 ± 6.7 and 59.1 ± 7.1 years, respectively (p > 0.05). Pre-SRP mean retinal sensitivities of the lower nasal quadrant in groups 1 and 2 were not different statistically (p > 0.05). Post-SRP mean retinal sensitivity of the lower nasal quadrant was significantly higher in group 2 than group 1. Moreover, mean defect has been found to be lower in group 2 (p < 0.05). The coefficient of variation for pre-SRP retinal sensitivity measurements were 7.9 and 7.6% for groups 1 and 2, respectively (p > 0.05). The coefficient of variation for post-SRP retinal sensitivity measurements were 3.8 and 2.1% for groups 1 and 2, respectively (p < 0.05). Conclusion: SRP treatment with 300-µm diameter laser spots may yield more reproducible visual field data than that with 500-µm diameter laser spots. Moreover, the improvement in the retinal sensitivity of the patients with branch retinal vein occlusion is more marked in case where 300-µm laser spots are used.

A Randomized, Controlled Trial to Investigate the Effect of Ciclesonide and Beclomethasone Dipropionate on Eye Lens Opacity

Background. Inhaled corticosteroids (ICS) are recommended first-line therapy for the treatment of persistent asthma. However, reports from observational studies have suggested that the use of ICS may be associated with systemic adverse events, such as glaucoma and cataract (opacity of the lens) formation. Objective. To compare two ICS over 1 year regarding the formation/progression of lenticular opacities in patients with asthma. Methods. Adults (≥ 18 years of age) with moderate-to-severe asthma were randomized to ciclesonide 640 μ g/day (n = 785) or beclomethasone dipropionate 640 μ g/day (n = 783) in a multinational, double-blind, active-controlled, parallel-group study. The primary endpoint was the occurrence of a positive Class I grading shift (increase [worsening] in Lens Opacities Classification System [LOCS] III score of ≥ 0.5 for nuclear opalescence, ≥ 0.8 for cortical opacification, or ≥ 0.5 for posterior subcapsular opacification, or cataract surgery) in either eye at any visit over the 12-month, double-blind treatment period. Results. Mean changes (± standard error) in nuclear opalescence and cortical and posterior subcapsular opacification were small and similar between groups (ciclesonide 640 μ g/day: 0.10 ± 0.02, 0.07 ± 0.02 and 0.04 ± 0.01, respectively; beclomethasone dipropionate 640 μ g/day: 0.11 ± 0.02, 0.09 ± 0.02 and 0.03 ± 0.01, respectively). Class I shifts were observed in 34.3% versus 36.8% of ciclesonide-treated and beclomethasone dipropionate-treated patients, respectively. Ciclesonide 640 μ g/day was non-inferior to beclomethasone dipropionate 640 μ g/day regarding Class I shifts (risk ratio of ciclesonide to beclomethasone dipropionate, 0.940 [95% confidence interval, 0.820–1.077]); the 95% confidence interval upper bound was lower than the pre-specified non-inferiority bound of 1.333 (p < 0.0001), thereby excluding the possibility of higher risk ratio values. Conclusions. Mean changes in LOCS III scores were very small in both groups. Treatment with ciclesonide 640 μ g/day or beclomethasone dipropionate 640 μ g/day for 1 year has a minimal impact on lenticular opacities development and/or progression.

Estimate of radiation dose to the lens in balloon sinuplasty

To estimate radiation dose to the lens during fluoroscopy-assisted balloon dilation of sinus ostia and to estimate the length of fluoroscopy time that will be tolerated. Radiation dose to the lens per unit fluoroscopy time was extrapolated from published data in fluoroscopically-guided balloon dacrocystoplasty. Mean exposure varies from 0.041 (right eye) to 0.284 (left eye) mGy/sec (P = 0.037) because the left eye is closer to the radiation source during the lateral projection. Threshold for lenticular opacity has been estimated as 500 mGy, which would be attained in the left eye after approximately 29 minutes of fluoroscopy. The lens may tolerate <30 minutes of fluoroscopy during balloon sinuplasty. The left eye receives a potentially greater radiation dose because of its proximity to the source in the lateral projection. Dedicated studies are indicated to specifically examine this issue during balloon sinuplasty.

Prevention of selenite-induced cataractogenesis in Wistar rats by the polyphenol, ellagic acid

The present study sought to evaluate the efficacy of the naturally-occurring polyphenol, ellagic acid, in preventing selenite-induced cataractogenesis. In the present study, Wistar rat pups were divided into 3 groups of 15 each. Group I (normal) rats received an intraperitoneal (i.p.) injection of normal saline on postpartum day 10; group II (cataract-untreated) rats received a single subcutaneous (s.c.) injection of sodium selenite (19μmol/kg body weight) on postpartum day 10; group III (cataract-treated) pups received a single s.c. injection of sodium selenite on postpartum day 10 and intraperitoneal injections of ellagic acid (200mg/kg body weight) on postpartum days 9–14. At the end of the study period (30th postpartum day), slit-lamp examination of both eyes of each rat pup revealed no lenticular opacification (cataract stage 0) in all eyes of group I pups, definite nuclear cataracts (stages 4–6) in the eyes of all (100%) group II rat pups and no lenticular opacification in eight (53%) and mild lenticular opacification (cataract stages 1–3) in seven (47%) of group III rats (changes in group II vs group III, P<0.01). The mean activities of the antioxidant enzymes catalase, glutathione peroxidase, superoxide dismutase and glutathione-S-transferase were significantly lower in lenses of Group II rats than in Group I or Group III rat lenses. In addition, the mean levels of GSH in lenses and erythrocytes were also significantly lower in Group II rats than in Group I or Group III rats. Conversely, the mean concentration of MDA (an indicator of lipid peroxidation) in lenses and erythrocytes was found to be significantly higher in Group II rats than that in Group I or Group III rats. Also, the mean concentration of calcium was found to be significantly higher in lenses of Group II rats than in those of Group I and Group III rats. The results suggest that ellagic acid can prevent or retard experimental selenite-induced cataractogenesis in Wistar rats. This protective effect in rat lenses appears to occur by maintaining the antioxidant defense system and inhibition of lipid peroxidation.

Recessive Congenital Total Cataract with Microcornea and Heterozygote Carrier Signs Caused by a Novel Missense CRYAA Mutation (R54C)

To determine the genetic basis for congenital total white cataract with microcornea in three affected siblings. Prospective interventional case series. Clinical ophthalmic examination, venous blood sampling for linkage analyses, and diagnostic testing of identified candidate gene(s). Three siblings had congenital total white cataract with microcornea; the parents and seven other siblings were asymptomatic. Linkage analysis mapped the phenotype to Hsa 21q22.3, the region of the gene for the alpha-A component of alpha-crystallin (CRYAA), with a logarithm of odds (LOD) score of 2.5. Diagnostic CRYAA sequencing revealed a novel homozygous nonsense mutation (R54C) in the three affected individuals only. One other sibling and the two parents were heterozygotes; these individuals had punctuate lenticular opacities evident by careful slit-lamp biomicroscopy which were not present in the noncarriers, all of whom had unremarkable ophthalmic examinations. R54C is the second reported recessive CRYAA mutation associated with congenital cataract and the first with described morphology: punctuate lenticular opacities in carriers and congenital total white cataract with microcornea in homozygotes. The microcornea may have been caused by an inductive effect on the developing cornea from the abnormal lens and/or reduced CRYAA molecular chaperoning of the cornea.