Andrew W. Eller

Age-related maculopathy: a genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions.

Age-related maculopathy (ARM), or age-related macular degeneration, is one of the most common causes of visual impairment in the elderly population of developed nations. In a combined analysis of two previous genomewide scans that included 391 families, containing up to 452 affected sib pairs, we found linkage evidence in four regions: 1q31, 9p13, 10q26, and 17q25. We now have added a third set of families and have performed an integrated analysis incorporating 530 families and up to 736 affected sib pairs. Under three diagnostic models, we have conducted linkage analyses using parametric (heterogeneity LOD [HLOD] scores under an autosomal dominant model) and nonparametric (Sall statistic) methods. There is ongoing evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. If we treat the third set of families as a replication set, then two regions (10q26 and 17q25) are replicated, with LOD scores >1.0. If we pool all our data together, then four regions (1q31, 2q14.3, 10q26, and 17q25) show HLOD or Sall scores > or =2.0. Within the 1q31 region, we observed an HLOD of 2.72 (genomewide P=.061) under our least stringent diagnostic model, whereas the 17q25 region contained a maximal HLOD of 3.53 (genomewide P=.007) under our intermediate diagnostic model. We have evaluated our results with respect to the findings from several new independent genomewide linkage studies and also have completed ordered subset analyses (OSAs) with apolipoprotein E alleles, smoking history, and age at onset as stratifying covariates. The OSAs generate the interesting hypothesis that the effect of smoking on the risk of ARM is accentuated by a gene in the 10q26 region--a region implicated by four other studies.

Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions.

PURPOSE We seek to identify genetic loci that contribute to age-related maculopathy susceptibility. METHODS Families consisting of at least two siblings affected by age-related maculopathy were ascertained using eye care records and fundus photographs. Additional family members were used to increase the power to detect linkage. Microsatellite genotyping was conducted by the National Heart, Lung and Blood Institute Mammalian Genotyping Service and the National Institutes of Health Center for Inherited Disease Research. Linkage analyses were conducted with parametric (autosomal dominant; heterogeneity lod score) and nonparametric methods (S(all) statistic) using three diagnostic models. False-positive rates were determined from simulations using actual pedigrees and genotyping data. RESULTS Under our least stringent diagnostic model, model C, 860 affected individuals from 391 families (452 sib pairs) were genotyped. Sixty-five percent of the affected individuals had evidence of exudative disease. Four regions, 1q31, 9p13, 10q26, and 17q25, showed multipoint heterogeneity lod scores or S(all) scores of 2.0 or greater (under at least one model). Under our most stringent diagnostic model, model A, the 1q31 heterogeneity lod score was 2.46 between D1S1660 and D1S1647. Under model C, the 17q25 heterogeneity lod score at D17S928 was 3.16. Using a threshold of 1.5, additional loci on chromosomes 2 and 12 were identified. CONCLUSIONS The locus on chromosome 1q31 independently confirms a report by Klein and associates mapping an age-related maculopathy susceptibility gene to this region. Simulations indicate that the 1q31 and 17q25 loci are unlikely to be false positives. There was no evidence that other known macular or retinal dystrophy candidate gene regions are major contributors to the genetics of age-related maculopathy.

Migration of silicone oil into the brain: a complication of intraocular silicone oil for retinal tamponade

PURPOSE To report a case in which intravitreal silicone oil migrated along the intracranial portion of the optic nerve and into the lateral ventricles of the brain after the repair of a retinal detachment secondary to cytomegalovirus retinitis. METHODS A 42-year-old man with acquired immunodeficiency syndrome (AIDS) developed a rhegmatogenous retinal detachment in his left eye secondary to a cytomegalovirus infection of the retina. The detachment was repaired using 5000 cs intraocular silicone oil for a long-term tamponade. Subsequently, the affected eye developed glaucoma, which was poorly controlled. Fifteen months after the retinal surgery, he developed a peripheral neuropathy that was thought to be AIDS related. Computed tomography and magnetic resonance imaging of the head were performed to investigate the neuropathy. RESULTS The patient was found to have a foreign substance within his lateral ventricles that shifted with position and was identical with respect to its imaging properties to the remaining intraocular silicone oil. Additional material was found along the intracranial portion of his optic nerve. CONCLUSION Under certain circumstances, intraocular silicone oil may migrate out of the eye, along the intracranial portion of the optic nerve, and into the lateral ventricles of the brain.

Serous retinal detachment resembling central serous chorioretinopathy following organ transplantation

Two patients developed unilateral serous retinal detachments of the macula resembling idiopathic center serous chorioretinopathy within 9 months of cardiac transplantation, while one renal transplant recipient developed bilateral serous detachments within 6 months of surgery. In two cases (three eyes), dense, yellow, fibrlin-like exudates were present in the subretinal fluid. At the time of presentation, each of the three patients had a modest elevation of blood urea nitrogen. Laser photo-coagulation was performed in three eyes with limited success, although ultimately the detachments resolved leaving only mild visual impairment (6/9 vision). The differential diagnosis of visual loss in the transplant population includes serous detachment of the sensory retina as well as more serious chorioretinal infections related to immunosuppression.

Quantitated Trauma Following Radial Keratotomy in Rabbits

Radial keratotomy was performed in 33 rabbits using an eight-incision technique. At various postoperative intervals up to 90 days, these eyes were enucleated and subjected to increasing quantitated trauma until ocular rupture occurred. Control animals (13 eyes) were subjected to similar trauma. The eyes that had surgery required approximately 50% of the control energy to rupture over the 90-day period (P less than 0.001). Corneal microperforations at surgery greatly increased the trauma risk (P = 0.02). Consistent rupture patterns resulted, both grossly and microscopically.

Prevalence of lens changes in Ukrainian children residing around Chernobyl.

The objective of this study is to determine the prevalence and characteristics of lens changes in the eyes of a pediatric population, 5-17 y old, living in the permanent control zone around the Chernobyl nuclear reactor and to compare these findings with those from an unexposed control population. A total of 1,787 children are reported on (996 exposed and 791 unexposed). Over three-quarters of the subjects examined in this study show a form of minor change, termed focal lens defect, in the cortical and/or nuclear portions of the lens of the eye. The exposed group shows a small (3.6%), but statistically significant excess (p = 0.0005) of subclinical posterior subcapsular lens changes similar in form to changes identified in atomic bomb survivors. These posterior subcapsular changes tend to occur in boys 12-17 y old and in exposed children who report consuming locally grown mushrooms on a regular basis.

Prediction of Visual Recovery After Scleral Buckling of Macula-off Retinal Detachments

Patients with rhegmatogenous retinal detachments involving the fovea have visual loss that may not be recoverable despite anatomically successful surgery. Few guidelines exist to predict ultimate visual outcome with any certainty. We found that despite macular detachment, a device commonly used to predict visual acuity in cataractous eyes, the Potential Acuity Meter (Mentor O & O, Inc., Norwell, Massachusetts), provided acuity measurements even when Snellen visual acuity levels were poor or unmeasurable. In a study of 50 consecutive patients with clear media, we investigated a possible correlation between postoperative Snellen visual acuity with the preoperative Potential Acuity Meter results. We found that actual visual improvement correlated well with potential visual improvement as determined by Potential Acuity Meter measurements (R = .92). Preoperative assessment of patients with this device was a better predictor of final visual outcome than preoperative Snellen visual acuity, the extent of retinal detachment, or the duration of the retinal detachment by history.

Melanocytoma of the Ciliary Body and Iris

A 29-year-old woman had a pigmented ciliary body mass that extended through the iris into the anterior chamber. On the basis of clinical findings and ancillary diagnostic studies, the clinical diagnosis was malignant melanoma of the ciliary body. The enucleated eye showed the tumor to be composed of cells identical to those of a melanocytoma of the optic disk.

The Role of Ciprofloxacin in Endophthalmitis Therapy

Ciprofloxacin has been proposed for the systemic treatment of endophthalmitis. We studied the role of therapy based on the susceptibility of actual bacterial isolates and developed a system for assessing this susceptibility in endophthalmitis. Susceptibility testing was performed on 68 bacterial isolates from 66 patients with endophthalmitis. Our results indicated that, on the basis of a vitreous ciprofloxacin concentration of 0.25 microgram/ml, only 41 of 68 isolates (60%) would be inhibited by systemic therapy. All gram-negative bacteria (six of six) would be inhibited, whereas gram-positive bacterial susceptibility was variable. We concluded that systemic ciprofloxacin alone should not be administered empirically but it could provide an adjunct for treating selective cases of bacterial endophthalmitis. Bacterial susceptibility should be assessed on a blood serum standard of 0.25 microgram/ml instead of 1.0 microgram/ml.

Non-Mydriatic Panoramic Fundus Imaging Using a Non-Contact Scanning Laser-Based System

BACKGROUND AND OBJECTIVE A non-contact scanning laser-based retinal imaging system produces a 200 degrees wide-field panoramic image of the fundus through the novel use of a large elliptical mirror. The authors investigated whether accurate diagnoses could be made from these images alone. PATIENTS AND METHODS Images were obtained from both eyes of arbitrarily selected patients and were retrospectively reviewed by retinal specialists. Each physician made a diagnosis, suggested the follow-up interval, and determined whether any intervention was needed based solely on image review. Diabetic retinopathy was categorized as background retinopathy only, preproliferative retinopathy, maculopathy, and proliferative retinopathy. The results of the image review were then compared with the results of clinical examination, and the sensitivity and specificity of the review were calculated. RESULTS The correct overall diagnosis was made by the two specialists in 87% and 77% of cases, respectively; the specificity and sensitivity each averaged 76%. Follow-up interval recommendations from image review matched those made on clinical examination in 86% of cases. Diabetic retinopathy was correctly identified as a general diagnosis with a sensitivity of 94% and the follow-up recommendations corresponded to the clinical recommendations in 82%. Sixty-two percent of the images were judged to be of good quality or better, with only 6.4% deemed unreadable. Iris color did not influence image quality. CONCLUSION The non-contact scanning laser-based retinal imaging system provides images of sufficient resolution and clarity to make accurate general diagnoses in a high percentage of cases. Its use as a screening device for specific diseases is feasible and merits further study.