Visual Morbidities among Patients at a Geriatric Center in Southwest Nigeria and the Merits of Designated Geriatric Health Care Centers Incorporating Eye Care Services.

BACKGROUND: : Visual morbidities increase the burden of care and negatively impact the quality of life of older people. Few empirical reports exist on the visual status of older Nigerians. AIM: This study describes the visual morbidities and determinants of visual impairment among persons aged 60 years and above who presented at a geriatric center in southwestern Nigeria and discusses the merits of focused geriatric care at a single location. MATERIALS AND METHODS: Data were obtained from electronic health records and case files of 628 older patients (≥60 years) who attended the facility between January 1, 2014 and December 31, 2018. Data extracted included, age, sex, married status, occupational status, visual acuity, eye diagnoses, eye medications, previous surgeries, and anthropometric measurements. RESULTS: Mean age of patients was 70.1 ± 7.4 years and 378 (60.2%) were females. Two out of every three patients had more than one visual diagnosis. Significantly, glaucoma (P < 0.001) and cataract (P = 0.01) were common among men, whereas dry eye syndrome (P < 0.001) and allergic conjunctivitis (P = 0.01) were common in women. Antiglaucoma medications (55.8%) were the commonest medications used and 21.0% had previous eye surgery. Assessment of presenting visual acuity demonstrated that 28.7% of patients had moderate-severe visual impairment (MSVI) in both eyes at presentation while 10.3% were bilaterally blind. Increasing age (P < 0.001) and male sex (P = 0.01) were the factors significantly associated with blindness. CONCLUSION: MSVI and blindness were common in our setting with glaucoma and cataract being the most prevalent associated diagnosis. Information obtained should stimulate advocacy for the prompt management of preventable causes of poor vision in older Nigerians.

A 5-YEAR REVIEW OF ULTRASONOGRAPHIC EVALUATION OF OCULAR DISEASES AT THE UNIVERSITY COLLEGE HOSPITAL IBADAN, SOUTH-WEST, NIGERIA.

BACKGROUND: Orbito-ocular diseases are a major public health issue, often causing visual impairment with serious socioeconomic implications on individual lives. Ocular ultrasonography is an invaluable diagnostic tool when clinical examination of the ocular fundus is difficult. OBJECTIVES: To describe the indications, sonographic findings, and contribution of orbito-ocular ultrasonography to the management of orbito-ocular diseases in the University College Hospital, Ibadan. MATERIALS AND METHODS: A retrospective review of B-mode ocular ultrasound findings and hospital data of all patients referred to the Radiology department of the University College Hospital, Ibadan for ocular Ultrasound between January 2014 - December 2018. RESULTS: There were 142 patients, aged 1-85 years, (median age =28 years). 72 (50.7%) patients were under 30 years of age, and 50 (35.2%) were pediatric cases. Male to female ratio was 1.84:1. The commonest presenting complaint was blurred vision in 97 (68.3%) cases, followed by eye trauma in 54 (38.0%). B-mode Ultrasound, demonstrated cataract in 63 (44.4%,) cases, vitreous hemorrhage in 42 (29.6%), retinal detachment in 27 (19.0%), vitreous detachment in 19 (13.4%), normal findings in 17 (12%) and orbital tumors in 13 (9.2%) patients. B-mode ultrasound scan and clinical diagnosis demonstrated good agreement in 91 /142 cases (64.1%), partial agreement in 23/142 (16.2%) cases, and no agreement in 28 (19.7%). Kappa agreement scores, K were 74.3% and 70.9%, for ruptured globe and cataract respectively. CONCLUSION: Orbito-ocular ultrasonography contributes significantly to the diagnosis of orbito-ocular disease and shows good correlation with clinical diagnoses. However, a future study with larger numbers is required.

Vision-related quality of life assessment of patients attending a geriatric centre in south-west Nigeria

According to World Health Organization, health not only refers to the absence of physical diseases, but also includes psychological and social well-being of individuals.[1] Quality of life (QoL) on the other hand, lacks a single, universally accepted definition.[2] However, QoL may be defined subjectively as "an individual's perception of his/her life in the context of the culture and value system in which they live, and in relation to their goals, expectations, standards and concerns.[3] QoL also has an objective component which can be measured objectively using validated instruments (e.g. questionnaires) in which a score is assigned to specific indices or characteristics in different domains along a scale in a continuum.[4],[5],[6]Visual function is important for optimal orientation in functional and social life and has effects on physical, psychological, mental and emotional well-being of the individual.[7] Visual function therefore is a domain under which QoL may be assessed. This is referred to as vision-specific or vision-related QoL. The National Eye Institute Visual Function Questionnaire (NEI-VFQ) is an example of an instrument designed and validated for the objective assessment of vision-specific QoL.[8]Broman et al.[9] revealed that a visual acuity of at least 6/12 was found to negatively impact on n individual's quality of life. This was also reiterated by Bekibele et al.[10] The Proyecto VER study[9] observed that visual impairment was associated with a decrease in the quality of life among elderly patients, and that the severity of ocular diseases was related to the level of visual impairment. In relation to persons with no visual impairment, persons with bilateral mild and unilateral or bilateral moderate or severe visual impairment report greater difficulties in performing most vision-dependent daily activities, experience vision-related dependency and poorer vision-related mental health.[11]Ee Munn Chia et al.[12] further disclosed that the impact of visual impairment on mental domains was much greater compared to co-existing medical conditions like stroke.Therefore, data is needed on the effect of ocular diseases on vision-related quality of life among the elderly for the purpose of making recommendations for improved eye care with resultant improvement in their quality of life

Predictors of outcome in 101 patients requiring emergent thoracotomy for penetrating pulmonary injuries.

BACKGROUND: Operative interventions are uncommonly required for penetrating pulmonary injuries. Similarly, because their incidence is low, few series appear sporadically in the literature. Objectives of this study are to identify predictors of outcome for patients requiring emergent thoracotomy for penetrating pulmonary injuries and evaluate the use of tissue sparing versus resective techniques for their management. STUDY DESIGN: This is a retrospective 169-month study of all patients with penetrating pulmonary injuries requiring thoracotomy. The main outcome measures are: physiologic parameters, AAST-OIS injury grade, surgical procedures and mortality. Statistical analysis includes univariate and stepwise logistic regression. RESULTS: 101 patients required thoracotomy for penetrating pulmonary injuries. Mechanism of injury includes: gunshot wounds (GSW)-73 (72%), stab wounds (SW)-28 (33%). Mean systolic BP 97 ± 47, mean HR 92 ± 47, and mean admission pH 7.22 ± 0.17. Mean RTS 6.25 ± 2.7, mean ISS 36 ± 22. The mean estimated blood loss (EBL) was 5277 ± 4955 mls. Predictors of outcome are: admission pH (p = 0.0014), admission base deficit (p < 0.0001), packed red blood cells (PRBCs) transfused (p = 0.023), whole blood transfused (p < 0.01). A total of 143 procedures were required in 101 patients: tissue sparing 114 (80%) versus resective procedures 29 (20%). Only pneumonectomy (p = 0.024) predicted outcome. Overall survival 64/101-64%. American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) injury grades I-III versus IV-VI predicts survival (p < 0.001). Stepwise logistic regression identified AAST-OIS injury grades IV-VI (p = 0.007; OR 6.38 [95% CI 1.64-24.78]), intraoperative dysrhythmias (p = 0.003; OR 17.38 [95% CI 2.59-116.49]) and associated cardiac injuries (p = 0.02; OR 8.74 [95% CI 1.37-55.79]) as independent predictors of outcome. CONCLUSIONS: Predictors of outcome for penetrating pulmonary injuries requiring thoracotomy are identified and must be taken into account in their operative management. Tissue sparing techniques-stapled pulmonary tractotomy is once again validated, and it remains effective as the mainstay for their management; however, only pneumonectomy predicts outcome. AAST-OIS injury grades IV-VI predict outcome with higher injury grades requiring resective procedures.

Penetrating cardiac injuries: predictive model for outcomes based on 2016 patients from the National Trauma Data Bank.

BACKGROUND: Penetrating cardiac injuries are uncommon and lethal. The objectives of this study are to examine the national profile of cardiac injuries, identify independent predictors of outcome, generate, compare and validate previous predictive models for outcomes. We hypothesized that National Trauma Data Bank (NTDB) given its large number of patients, would validate these models. METHODS: The NTDB was queried for data on cardiac injuries, using survival as the main outcome measure. Statistical analysis was performed utilizing univariate and stepwise logistic regression. The stepwise logistic regression model was then compared with other predictive models of outcome. RESULTS: There were 2016 patients with penetrating cardiac injuries identified from 1,310,720 patients. Incidence: 0.16%. Mechanism of injury: GSWs-1264 (63%), SWs-716 (36%), Shotgun/impalement-19/16 (1%). Mean RTS 1.75, mean ISS 27 ± 23. Overall survival 675 (33%). 830 patients (41%) underwent ED thoracotomy, 47 survived (6%). Survival stratified by mechanism: GSWs 114/1264 (10%), SWs 564/717 (76%). Predictors of outcome for mortality-univariate analysis: vital signs, RTS, ISS, GCS: Field CPR, ED intubation, ED thoracotomy and aortic cross-clamping (p < 0.001). Stepwise logistic regression identified cardiac GSW's (p < 0.001; AOR 26.85; 95% CI 17.21-41.89), field CPR (p = 0.003; AOR 3.65; 95% CI 1.53-8.69), the absence of spontaneous ventilation (p = 0.008; AOR 1.08, 95% CI 1.02-1.14), the presence of an associated abdominal GSW (p = 0.009; AOR 2.58, 95% CI 1.26-5.26) need for ED airway (p = 0.0003 AOR 1386.30; 95% CI 126.0-15251.71) and aortic cross-clamping (p = 0.0003 AOR 0.18; 95% CI 0.11-0.28) as independent predictors for mortality. Overall predictive power of model-93%. CONCLUSION: Predictors of outcome were identified. Overall survival rates are lower than prospective studies report. Predictive model from NTDB generated larger number of strong independent predictors of outcomes, correlated and validated previous predictive models.

Oxidative stress markers and genetic polymorphisms of glutathione S-transferase T1, M1, and P1 in a subset of children with autism spectrum disorder in Lagos, Nigeria.

BACKGROUND: The role of oxidative stress has been identified in the development of autism spectrum disorder (ASD), and polymorphisms of glutathione S-transferase have been associated with some diseases linked to oxidative stress. Hence, we evaluated the serum levels of oxidative stress markers and investigated genetic polymorphisms of glutathione S-transferase associated with autism. MATERIALS AND METHODS: Forty-two children clinically diagnosed with ASD using the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and a clinical interview were included in the study. Twenty-three age-matched controls without any known genetic/developmental disorder were also recruited. Oxidative stress markers along with the genetic polymorphisms of glutathione S-transferase were determined. RESULTS: Reduced glutathione in ASD patients was significantly lower than the control (P = 0.008), whereas other oxidative stress markers measured were not significantly different in both the control and case populations. The frequencies of GSTT1 and GSTM1 null genotypes were lower among the controls compared with the cases, however, no association risk was observed. The observed risk of carrying Val/Val genotype among the cases was approximately six times that of the controls. CONCLUSION: Individuals with ASD showed a significant diminished level of reduced glutathione, however, the distribution of GSTT1, GSTM1, and GSTP1 polymorphisms was not found to be associated with autism in this study population.

TIME OF PRESENTATION OF STROKE PATIENTS FOR CT IMAGING IN A NIGERIAN TERTIARY HOSPITAL.

BACKGROUND: Neuroimaging is the cornerstone for guiding thrombolytic and interventional therapy for stroke. Beneficial outcome can only be obtained within a rather short time of less than 3-4.5 hours of symptom onset. Challenges in developing countries like Nigeria often lead to delayed presentation of stroke patients in hospitals. We sought to study the time and pattern of presentation of stroke patients for CT imaging in a Nigerian tertiary hospital. METHODS: Of the 271 stroke patients who had cranial CT between 2008 and 2010, eighty-three (30.6%) with full retrievable CT records, were included in this study. They were categorized into six time groups cross-tabulated with their CT findings. RESULTS: Forty-two patients (50.6%) had cerebral infarction while 23 (27.7%) had haemorrhagic stroke. However, 18 (21.7%) patients had apparently normal CT findings. The mean presentation time for CT imaging was 70 hours (SD ±94 hours). Only 31% of all stroke patients presented for CT imaging within 12 hours, and none, within 3 hours. Forty-six percent did not present within 24 hours of symptom onset. Significantly more patients with ischemic stroke (72.3%) than hemorrhagic stroke (27.7%) presented after 12 hours of ictus (X(2) = 4.027 d=1, P =0.045). Age (X(2)=0.008, P =0.931) and gender (X(2)1.742, d=1,P =0.187) had no statistically significant relationship with the time of presentation for CT imaging. CONCLUSION: None of our patients met the time criteria for thrombolytic therapy. Ischemic stroke patients presented for imaging later than patients with intracerebral haemorrhage. There is a need to increase the awareness regarding early recognition, presentation and diagnosis of stroke for timely intervention in Nigeria.

Risk factors for pterygium recurrence after surgical excision with combined conjunctival autograft (CAG) and intraoperative antimetabolite use.

BACKGROUND: To identify the determinants of recurrence following primary pterygium excision combined with conjunctival autograft (CAG) and intraoperative use of Mitomycin C (MMC) or 5-Fluorouracil (5-FU). METHODS: A randomized controlled clinical trial comparing 5-FU (50 mg/ml) plus CAG versus MMC (0.01%) plus CAG in preventing recurrence of primary pterygium following excision. RESULTS: A total of 80 eyes of 80 subjects were studied, with 46 eyes in the 5-FU group and 34 eyes in the MMC group. The mean age was 50.7 +/- 13.1 years with a male: female ratio of 0.95:1. Mean follow up period was 35.2 +/- 29.1 weeks. The overall recurrence rate was 10%, with a rate of 8.7% in the 5-FU group and 11.8% in the MMC group. The mean age of the patients who had a recurrence was 38.1 +/- 13.3 years compared to 52.1 +/- 12.4 years in those without a recurrence (p = 0.003). The median size of the pterygium in patients who had a recurrence was 3.2mm, while the median size in patients who did not have a recurrence was 3.0mm (p = 0.8). Five (12.8%) males had a recurrence compared to three (7.3%) females (p = 0.48); while 10.5% of fleshy pterygia recurred compared to none (0%) of the non-fleshy pterygia (p = 1.00). CONCLUSION: Younger age remains a risk factor for recurrence when both CAG and antimetabolites are combined in the treatment of pterygium, while the effect of gender, size and morphology of the pterygium may be diminished by such combination.

Computed tomography measurement of extra-ocular muscle diameters in a population of normal patients in a tertiary hospital in Nigeria.

BACKGROUND: Measurements of extraocular muscle diameter may be useful in diagnosis and as an outcome indicator in the assessment of treatment options in thyroid-associated ophthalmopathy. Racial differences are known to account for craniofacial variations and orbital sizes. OBJECTIVE: To determine the normal diameters of extra-ocular muscles using computed tomography in a homogeneous, group of hospital patients in a tertiary hospital in Nigeria. MATERIAL AND METHOD: The maximum diameters of extra-ocular muscles were measured for 182 normal patients on thin slice reconstructed coronal computed tomography images. The effects of age and sex were determined. RESULT: Normal ranges for the diameters (mean + 2 SDs) of extraocular muscles were 4.5 + 1.2 mm for medial rectus, 4.9 + 2.1 mm for lateral rectus, 4.8 + 1.6 mm for inferior rectus and 4.0 + 1.5 mm for the superior group. The mean diameter of the extra-ocular muscles of male patients was not significantly larger than that of female patients (p > 0.05). There was a small but positive correlation between age and diameter of each extra-ocular muscle except in the left medial rectus and right lateral rectus muscles (P < 0.05). CONCLUSION: These normative values may serve as radiological reference values in the assessment of changes in size and suspected enlargement of the extraocular muscles in Nigerian patients. They may also be extrapolated to other Black African patients, until population studies become available.

Non-glaucomatous optic neuropathy in ibadan: extrapolations to healthcare funding in Nigeria.

BACKGROUND: Optic neuropathy is not a diagnosis in itself, as potential aetiologies are myriad. A pilot study conducted in the Eye Clinic, University College Hospital, Ibadan, between September 2007 and November 2009, showed that 46.8% of new cases presenting to the neuroophthalmology unit, had non-glaucomatous optic neuropathy (NGON) in which, the precise aetiology of optic neuropathy was never diagnosed. METHODS: All cases of NGON, seen in the neuro-ophthalmology unit, between September 2007 and June 2014 were analyzed to determine common aetiologies and identify the difficulties encountered in their investigation or management. RESULTS: There were 159 cases of NGON. The age range was 6 months to 87 years (mean 39.0, SD 21.3). Male: Female ratio was 1.2: 1, and the commonest diagnosis was optic atrophy of unknown aetiology. Challenges identified included difficulty obtaining recommended radiological and serological investigations, as well as no access to genetic studies and high loss to follow-up. CONCLUSION: There are major constraints in the investigation of patients presenting with optic nerve disease in Ibadan, despite the prevalence of NGON as a major cause of visual disability among neuro-ophthalmic patients in this setting. Diagnostic constraints must be addressed, to facilitate neuroophthalmology patient care, within our limited resources.

Squamous papillomas of the conjunctiva: a retrospective clinicopathological study.

BACKGROUND: There is very limited literature on squamous papillomas of the conjunctiva from Nigeria and sub-Saharan Africa. In an attempt to contribute to the literature on the subject, we studied the clinicopathological characteristics of patients histologically diagnosed with squamous papilloma of the conjunctiva in Ibadan, Nigeria. MATERIALS AND METHODS: Clinical and pathological records of patients with histological diagnosis of squamous papilloma of the conjunctiva made in the Department of Pathology, University College Hospital, Ibadan, between January 1985 and December 2004, were reviewed. RESULTS: There were totally 26 cases. Patients' ages ranged from 2 to 58 years with a mean age of 32 years. Male to female ratio was 1.4:1. Size of tumors ranged from 2 to 10 mm. Duration of presenting complaints was from 2 months to 10 years. The lesions in 10 cases were located in the medial canthus, at or close to the limbus in another 10 cases, and in the tarsal conjunctiva in a single case. Five cases had no documentation of location. Sixteen cases (61.5%) had multiple papillomas. Four cases had a history of chemical injury (alkaline based - hair relaxer in a single case, acid based - wet cell car battery fluid in two cases, and unknown chemical in a single case) preceding the lesion by at least 6 weeks. Fourteen cases had koilocytosis on histology suggestive of Human Papilloma Virus (HPV) etiology. HIV screening test was negative in the three patients who had the screening done. Preoperative clinical diagnosis was squamous papilloma in 16 cases, pterygium in 6 cases and squamous cell carcinoma in 2 cases. CONCLUSION: In the environment where we practice, conjunctival squamous papilloma occurs most commonly in the fourth decade of life. Only very few cases are submitted for histological diagnosis. HPV infection and chemical injury are the main etiology. We strongly advocate that all excisions of the conjunctiva, irrespective of the clinical impression, should be submitted routinely for histological assessment.

Prevalence and correlates of psychiatric morbidity among caregivers of children and adolescents with neuropsychiatric disorders in Nigeria.

OBJECTIVE: To screen for psychiatric morbidity among caregivers of patients attending a child and adolescent psychiatric clinic. METHOD: A total of 155 patients and their caregivers were consecutively recruited over a 1 month period. Sociodemographic and clinical information on patients was obtained either from the hospital records or from the caregiver. Scoring on the Children's Global Assessment Scale (CGAS) was done by clinicians. The caregivers were administered a sociodemographic questionnaire, GHQ-12, Zarit Burden interview, and the Columbia Impairment Scale. RESULTS: Most caregivers observed in this study were females (80.5%) with mothers of the patients accounting for 78% of all the caregivers. A higher percentage of the patients were males (52.8%). Among the caregivers, 39.4% had GHQ Scores of 3 and above. Factors associated with psychiatric morbidity among caregivers include the high level of subjective burden of care, low level of functioning, high degree of impairment and low level of education among patients. CONCLUSION: The study reveals a high level of psychiatric morbidity among the carers of children and adolescents with mental health problems.

Orbital solitary fibrous tumor. Another rare case from Africa.

Solitary fibrous tumor (SFT) of the orbit, initially thought to be rare, is being increasingly documented in the medical literature. We here present the case of a 37-year-old Nigerian man who presented with left sided painless, vision-sparing proptosis. Cranial computed tomography scan showed a globular, left medial, orbital extraconal mass. The mass was excised, en bloc, via a medial orbitotomy procedure aided by left ethmoidectomy. Surgery was uncomplicated and histology of the excised tissue was reported as compatible with SFT. There was also a strong and diffuse immunostaining with CD 34. At 6-month follow-up, the left-sided proptosis has completely regressed. To the best of our knowledge, this is the second case of orbital SFT to be reported in an African.

Factors influencing time to diagnosis of childhood cancer in Ibadan, Nigeria.

BACKGROUND: Early diagnosis of cancer allows an opportunity for timely treatment while disease burden is in its earliest stages. Unfortunately, late presentation and delayed diagnosis of childhood cancers remains a problem in developing countries. OBJECTIVES: To describe the pre-diagnostic symptomatic intervals and the factors influencing these time intervals in childhood cancer at the University College Hospital, Ibadan, Nigeria. METHODS: Information was obtained from the case notes of children seen between March 2006 and August 2008. Information included socio-demographic variables, stage of the cancer, duration of illness at diagnosis and other health seeking activities. RESULTS: Sixty-four children (40 males, 24 females) were studied. Median overall lag time was 13.1 weeks; median parent delay was 2 weeks and median health system delay was 8.8 weeks. Median lag times were shortest in acute leukaemia (8.1 weeks) and Wilms. tumour (8.7 weeks) and longest in Hodgkin lymphoma (101.7 weeks). CONCLUSION: Lag times were longer than those in developed countries. Factors contributing to delayed diagnosis included delayed referral by doctors, seeking health care from alternate sources and financial constraints. Education of parents and physicians on early presentation and early referral for early diagnosis is recommended.

Clinical neuropsychiatric correlates and EEG findings among children with developmental disorders in Lagos, Nigeria.

OBJECTIVE: Developmental disorders with or without associated neuropsychiatric complications continue to be one of the major health problems in Africa. The grossly inadequate management/ rehabilitative facilities further worsen this. A prospective study aimed at finding the types of developmental disorders and associated neuropsychiatric complications among children aged

Enhanced crystallization of the Cys18 to Ser mutant of bovine gammaB crystallin.

The cysteine residues of the gamma crystallins, a family of ocular lens proteins, are involved in the aggregation and phase separation of these proteins. Both these phenomena are implicated in cataract formation. We have used bovine gammaB crystallin as a model system to study the role of the individual cysteine residues in the aggregation and phase separation of the gamma crystallins. Here, we compare the thermodynamic and kinetic behavior of the recombinant wild-type protein (WT) and the Cys18 to Ser (C18S) mutant. We find that the solubilities of the two proteins are similar. The kinetics of crystallization, however, are different. The WT crystallizes slowly enough for the metastable liquid-liquid coexistence to be easily observed. C18S, on the other hand, crystallizes rapidly; the metastable coexisting liquid phases of the pure mutant do not form. Nevertheless, the coexistence curve of C18S can be determined provided that crystallization is kinetically suppressed. In this way we found that the coexistence curve coincides with that of the WT. Despite the difference in the kinetics of crystallization, the two proteins were found to have the same crystal forms and almost identical X-ray structures. Our results demonstrate that even conservative point mutations can bring about dramatic changes in the kinetics of crystallization. The implications of our findings for cataract formation and protein crystallization are discussed.

Crystal cataracts: human genetic cataract caused by protein crystallization.

Several human genetic cataracts have been linked recently to point mutations in the gammaD crystallin gene. Here we provide a molecular basis for lens opacity in two genetic cataracts and suggest that the opacity occurs because of the spontaneous crystallization of the mutant proteins. Such crystallization of endogenous proteins leading to pathology is an unusual event. Measurements of the solubility curves of crystals of the Arg-58 to His and Arg-36 to Ser mutants of gammaD crystallin show that the mutations dramatically lower the solubility of the protein. Furthermore, the crystal nucleation rate of the mutants is enhanced considerably relative to that of the wild-type protein. It should be noted that, although there is a marked difference in phase behavior, there is no significant difference in protein conformation among the three proteins.

Molecular basis of a progressive juvenile-onset hereditary cataract.

In a recent paper, patients with a progressive juvenile-onset hereditary cataract have been reported to have a point mutation in the human gammaD crystallin gene (Stephan, D. A., Gillanders, E., Vanderveen, D., Freas-Lutz, D., Wistow, G., Baxevanis, A. D., Robbins, C. M., VanAuken, A., Quesenberry, M. I., Bailey-Wilson, J., et al. (1999) Proc. Natl. Acad. Sci. USA 96, 1008-1012). This mutation results in the substitution of Arg-14 in the native protein by a Cys residue. It is not understood how this mutation leads to cataract. We have expressed recombinant wild-type human gammaD crystallin (HGD) and its Arg-14 to Cys mutant (R14C) in Escherichia coli and show that R14C forms disulfide-linked oligomers, which markedly raise the phase separation temperature of the protein solution. Eventually, R14C precipitates. In contrast, HGD slowly forms only disulfide-linked dimers and no oligomers. These data strongly suggest that the observed cataract is triggered by the thiol-mediated aggregation of R14C. The aggregation profiles of HGD and R14C are consistent with our homology modeling studies that reveal that R14C contains two exposed cysteine residues, whereas HGD has only one. Our CD, fluorescence, and differential scanning calorimetric studies show that HGD and R14C have nearly identical secondary and tertiary structures and stabilities. Thus, contrary to current views, unfolding or destabilization of the protein is not necessary for cataractogenesis.