Carl Kupfer

1. Tamoxifen Retinopathy: A Clinicopathologic Report

Abstract A 57-year-old woman with metastatic breast carcinoma treated by surgery and high-dosage tamoxifen chemotherapy developed tamoxifen retinopathy characterized by white superficial retractile retinal lesions primarily in the paramacular area. At postmortem examination, the retinal lesions seen clinically were identified as being 3 to 10 microns in diameter in the macular area, and 30 to 35 microns in diameter in the paramacular area. The lesions were confined to the nerve fiber layer and inner plexiform layer and stained positive with stains for glycosaminoglycans. Electron microscopic examination revealed that the smaller lesions were intracellular and the larger lesions extracellular. The lesions were composed of randomly oriented branching electron dense 6-nm filaments accompanied by occasional electron dense coated vesicles measuring 60 to 70 nm in diameter. The lesions appeared to be occurring in axons and seemed to represent products of axonal degeneration.

OBSERVATIONS ON THE DEVELOPMENT OF THE ANTERIOR CHAMBER ANGLE WITH REFERENCE TO THE PATHOGENESIS OF CONGENITAL GLAUCOMAS

Abnormalities in neural crest cell migration may have a role in the pathogenesis of the congenital glaucomas, with or without changes in the gonioscopic appearance of the anterior chamber angle. Neural crest cells also contribute to the bones of the face, dental papilla, cartilage, bone, and meninges; this may explain the association of craniofacial, dental, and upper spinal malformations with some of the congenital glaucomas.

The Madurai Intraocular Lens Study II: Clinical Outcomes

PURPOSE To evaluate the safety and efficacy of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) compared with intracapsular cataract extraction with aphakic glasses (ICCE-AG). METHODS In a nonmasked randomized controlled clinical trial, 3,400 bilaterally vision-impaired patients aged 40 to 75 years with operable cataract were randomly assigned to receive either ICCE-AG or ECCE/PC-IOL at the Aravind Eye Hospital in India. The surgery was performed by one of four study surgeons. Patients were hospitalized for 5 postoperative days, with follow-up visits at 2, 6, and 12 months after discharge. Postsurgery evaluations were conducted by two independent study ophthalmologists. RESULTS At any single postoperative follow-up time point, there were no statistically significant differences of clinical relevance between treatment groups for any complication of a serious nature except cystoid macular edema, which was more common with ICCE (4.2% vs 1.6%). In general, whether of a trivial, intermediate, or serious nature, complication rates were low at each evaluation time point. Cumulatively, the incidence of serious complications of all types throughout the 1-year study period was 14.5% for patients in the ICCE-AG group and 7.7% in the ECCE group (P < .001). Best-corrected visual acuity of 20/40 or better at 12 months was attained by 90.7% of ICCE-AG patients and 96.3% of ECCE/PC-IOL patients (P < .001). CONCLUSION Although both operative procedures are safe and effective for cataract patients with bilateral impairment, ECCE/PC-IOL is superior to ICCE-AG in terms of both visual acuity restoration and safety.

The Histopathology of Pigmentary Dispersion Syndrome with Glaucoma

Iris tissue and trabecular meshwork, obtained at time of trabeculectomy, was studied using the light and electron microscope in a 54-year-old woman with pigmentary dispersion syndrome with glaucoma. The specific defect was a loss of the outer epithelial cells of the iris with marked thinning of the remaining outer layers so that the two-cell architecture of the iris epithelium was maintained. In addition, the radial muscle layer was increased in both number and size of muscle fiber. It would appear that the pigmentary dispersion syndrome may represent a congenital or developmental abnormality of the iris epithelium, or both, and that the glaucoma which occasionally occurs in conjunction with this syndrome is of the usual open-angle type.

Studies of aqueous humour dynamics in man. VI. Effect of age upon parameters of intraocular pressure in normal human eyes.

Abstract Parameters of aqueous dynamics have been evaluated for both eyes of each member of a group of young normal volunteers and of a group of old normal volunteers. In the old volunteers, the observed lower total facility is comprised of a lower true facility of outflow and a lower pseudofacility. The reduced outflow facility is partly counterbalanced by a lower aqueous flow. Also, in the older eyes, ocular rigidity is higher. Mean episcleral venous pressure is the same for the two groups. The major effect of age seen in this study is alteration of the function of the outflow pathways of the eye, with simultaneous, partially counter-balancing, decrease of aqueous production associated with decreased pseudofacility.

The Contralateral Eye in the Iridocorneal Endothelial (ICE) Syndrome

Examination of six cases of iridocorneal endothelial (ICE) syndrome revealed that all the patients had subclinical abnormalities in the fellow eye. Of the six, four patients had iris transillumination, four patients had significantly decreased outflow facility but without elevation of intraocular pressure, and all patients had corneal endothelial changes as noted by specular microscopy. The asymmetric rather than unilateral involvement and the similar histopathology to posterior polymorphous dystrophy suggested that these two diseases may share a common pathogenesis. The occurrence of features of Riegers syndrome and Axenfelds anomaly in association with posterior polymorphous dystrophy suggested the hypothesis that all these diseases may be characterized by abnormalities of tissues derived from neural crest cells. A unifying hypothesis is presented to explain this group of diseases involving the endothelial cells lining the anterior chamber, namely corneal and trabecular meshwork endothelium, anterior iris stroma and iris melanophores.

The Madurai Intraocular Lens Study. I: A randomized clinical trial comparing complications and vision outcomes of intracapsular cataract extraction and extracapsular cataract extraction with posterior chamber intraocular lens.

PURPOSE The Madurai Intraocular Lens Study (MIOLS) was designed to compare safety, efficacy, and quality of life outcomes after either intracapsular cataract extraction with aphakic glasses (ICCE-AG) or extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/ PC-IOL). METHODS The Madurai Intraocular Lens Study was a nonmasked randomized controlled clinical trial conducted at a single hospital. Thirty-four hundred patients with age-related cataracts and having a best-corrected visual acuity less than or equal to 20/120 in the better eye were randomly assigned to either of the two cataract operative procedures. The main clinical outcomes were safety (complication rates) and efficacy (best-corrected visual acuity at 1 year equal to or better than 20/40). In addition, a subset of 1,700 trial participants received questionnaires before surgery, at 6 months after surgery, and at 1 year after surgery to measure visual functioning and vision-related quality of life. RESULTS Details of study design, study organization, clinical and quality of life outcome variables, sample size calculations, patient eligibility criteria and recruitment, randomization and masking, participant flow, adherence to follow-up, quality assurance, and statistical methods are presented. CONCLUSIONS The Madurai Intraocular Lens Study has sufficient power to detect clinically significant differences between the treatment options. There were no statistically significant differences between the two treatment groups for any of the major study variables at baseline. A high level of quality assurance was maintained throughout the October 1993 to June 1996 study period. The results should be applicable to all settings where the requisite expertise and resources are present.

Progressive bilateral essential iris atrophy.

Bilateral progressive essential iris atrophy, more advanced in one eye than in the other, occurred in a 24-year-old white man. Histopathologic examination of the iris from the eye with the more advanced iris atrophy disclosed no vascular abnormalities in that the vessels were patent and appeared normal except for accumulated perivascular connective tissue. Fluorescein angiographic examination of the fellow eye that was undergoing the earliest changes of iris atrophy failed to reveal any vascular abnormalities. However, tonographic examination indicated a markedly decreased outflow facility. There does not appear to be any vascular abnormality involved in the pathogenesis.

The Madurai Intraocular Lens Study IV: posterior capsule opacification

PURPOSE To estimate the cumulative incidence of posterior capsule opacification 4 years after surgery in patients who participated in the Madurai Intraocular Lens Study and had extracapsular cataract extraction with posterior chamber intraocular lens implantation. METHODS In the Madurai Intraocular Lens Study, 1,700 patients with best-corrected visual acuity 20/120 or worse in the better eye had extracapsular cataract extraction with posterior chamber intraocular lens implantation, and 1,474 (86.7%) of these completed the 1-year follow-up examination. From this group of 1,474 pseudophakic patients, 400 were randomly selected for reexamination 4 years after the original surgery. The eye that was operated on was examined by an ophthalmologist who was involved in the 1-year follow-up examinations and posterior capsule opacification grading. A grading of I to III was used to reflect the degree of opacification. With grades II and III, posterior capsule opacification detectable with an undilated pupil was present in the central axis. RESULTS Three hundred twenty-seven (81.8%) of the selected population were examined between October 1997 and December 1998. Thirty-four (8.5%) were confirmed as being deceased, and 39 (9.8%) were unavailable for follow-up. The median age was 60 years, and 57.2% were women. The 4-year incidence of grade II or III posterior capsule opacification, including eyes already treated with laser capsulotomy, was 13.1% (95% confidence interval [CI], 9.7% to 17.3%). Each year of increased age was associated with a decreased risk of posterior capsule opacification (odds ratio, 0.96; 95% CI, 0.92 to 1.00). Based on best-corrected visual acuity of 20/40 or worse without co-existing pathology, the 4-year incidence of posterior capsule opacification was 13.5%. CONCLUSION Because patients with relatively mature cataracts routinely receive extracapsular cataract extraction with posterior chamber intraocular lens implantation instead of the traditional intracapsular extraction, the subsequent need for laser capsulotomy may be less than that anticipated, based on previous reports.

New Hypothesis on Anterior Chamber Developmental Anomalies Associated with Glaucoma

A most interesting group of congenital and developmental anomalies is that involving the structures forming the anterior chamber. In these anomalies, the cornea, iris, or trabecular meshwork are affected to varying degrees, and often there are elevations of intraocular pressure. A number of eponyms have been used for these malformations such as Axenfeld’s anomaly, Rieger’s anomaly, and Peter’s anomaly, as well as descriptive terms such as goniodysgenesis associated with hereditary juvenile glaucoma. Collectively, this group of conditions have been referred to as the anterior chamber cleavage syndrome. (10)