Bangerter foils in the treatment of moderate amblyopia.

PURPOSE: To investigate Bangerter foils as an alternative method of treating amblyopia. PATIENTS AND METHODS: Thirty-three amblyopic children with vision of 20/60 or better in the amblyopic eye were treated with Bangerter foils. The foils were used as primary treatment in 15 patients and after initial occlusion therapy in 18 patients. The Bangerter foils were worn fulltime on the spectacle lens in front of the dominant eye. The density of the foil was decreased as vision improved. RESULTS: Thirty-one patients had good compliance. All of these achieved 20/30 vision or better in the amblyopic eye with an average of 1.4 years follow-up after cessation of treatment. Over half retained 20/20 acuity. CONCLUSION: Bangerter foils are effective for treatment of amblyopia with 20/60 or better vision. They can be used as primary treatment or as alternative treatment in cases where patching therapy is not providing further benefit.

Stereopsis and binocular vision after surgery for unilateral infantile cataract.

PURPOSE: To assess the prevalence and level of binocular function in children with unilateral congenital or very early infantile cataract. METHODS: We retrospectively reviewed the charts of all patients with unilateral congenital or very early infantile cataract who underwent operation before 4 months of age, at the W. K. Kellogg Eye Center/University of Michigan Hospitals, from 1985 to 1995. Amblyopia was treated with a reduced patching schedule consisting of 1 hour per day per month of age for the first 6 months of life, in an attempt to improve binocular function by allowing more hours of binocular interaction during the presumed critical period for development of binocular cortical pathways. RESULTS: Thirteen patients met the inclusion criteria. Seven patients had persistent hyperplastic primary vitreous (PHPV) cataract and 6 had non-PHPV cataract. Overall, visual acuity of 20/80 or better developed in 69% of patients; 100% of eyes with non-PHPV cataract achieved visual acuity of 20/60 or better. Stereopsis of 400 arc seconds or better was detectable in 62% of patients, including 3 with PHPV cataract and 3 who required strabismus surgery in the first year of life. Three children had better than 150 arc seconds of stereopsis. The incidence of large-angle strabismus was 54%. CONCLUSIONS: Binocular cooperation, including gross and fine stereopsis, can develop in children with unilateral aphakia as a result of early removal of infantile cataracts. A less-strenuous patching schedule than has been historically advocated may foster this process, while restoring and maintaining good central visual acuity in patients with excellent compliance with contact lens and occlusion regimens.

Modulation of basic fibroblast growth factor effect by retinoic acid in cultured retinal pigment epithelium.

PURPOSE: We investigated the effect of retinoic acid (RA) on basic fibroblast growth factor (bFGF)-stimulated proliferation of cultured human retinal pigment epithelial (hRPE) cells and of 125I-bFGF-binding to the bFGF plasma membrane receptors of hRPE. METHODS: Proliferation of hRPE cells in the presence of increasing concentrations of bFGF and bFGF + RA was measured by 3H-thymidine incorporation into hRPE cells. To characterize bFGF receptors, hRPE cells were incubated at 4 degrees C with 125I-bFGF in the presence or absence of heparin. RESULTS: Basic-FGF stimulated 3H-thymidine incorporation into hRPE cells in a dose-dependent manner. RA inhibited bFGF-stimulated 3H-thymidine incorporation in the presence or absence of heparin. Increasing concentrations of unlabeled bFGF decreased the binding of 125I-bFGF to hRPE cells. Scatchared analysis indicated the presence of high and low affinity binding sites for bFGF with an apparent affinity Kd of 50 pM and 330 pM, respectively, and a binding capacity (Bmax) of 1.25 X 10(5) and 3.38 X 10(5) binding sites per cell. Inhibition of 125I-bFGF binding was also possible by the carboxyl-terminal region peptide fragment bFGF-(106-120)-NH2, but not amino-terminal region peptide fragment bFGF-(1-24)-NH2. The addition of heparin to the medium during binding studies did not prevent RA from inhibiting binding of 125I-bFGF to hRPE cells. Scatchard analysis demonstrated that, in the presence of heparin, there is a decrease in the number of high affinity binding sites (from 1.12 +/- 0.11 x 10(5) to 0.7 +/- 0.03 x 10(5) binding sites per cell, a reduction of 36.7 +/- 0.04%, n = 3, p < 0.05). There was no significant change in affinity constants. CONCLUSIONS: These results suggest that RA inhibits bFGF cell proliferation in hRPE cells by decreasing the bFGF receptor number.

Prevention of ornithine cytotoxicity by proline in human retinal pigment epithelial cells.

PURPOSE: To investigate the relationship between ornithine-delta-aminotransferase (OAT) deficiency and ornithine accumulation and the specific degeneration of retinal pigment epithelial (RPE) cells in gyrate atrophy. METHODS: Human RPE cells, human hepatoma cells, and human fibroblast cells were treated with 5-fluoromethylornithine (5-FMOrn), a specific irreversible inhibitor of OAT. Ornithine cytotoxicity was determined by using a [3H]thymidine incorporation assay and immunohistochemical staining for cytokeratin. The effects of various metabolites of ornithine and arginine, such as creatine, creatine phosphate, I-delta 1-pyrroline-5-carboxylic acid (L-P5C), and proline, which may be deficient in gyrate atrophy on RPE cell damage by ornithine, were determined by the same procedures. RESULTS: When the human RPE cells, HepG2 hepatoma cells, and WI-38 fibroblast cells were treated with 0.5 mM 5-FMOrn for 30 minutes, which inactivated OAT, ornithine exhibited severe time- and dose-dependent inhibition of DNA synthesis in the human RPE cells but not in the HepG2 hepatoma cells or WI-38 fibroblast cells. The inhibition of DNA synthesis was accompanied by drastic changes in morphologic appearance, disorganization of the cytoskeleton, and cell death. Ornithine or 5-FMOrn alone did not exhibit such cytotoxicity to the RPE cells. Proline prevented the cytotoxicity of ornithine. CONCLUSIONS: These findings suggest that an elevated level of ornithine combined with an increased sensitivity to ornithine as a result of OAT deficiency may be crucial to the specific RPE degeneration in gyrate atrophy. They suggest also that abnormalities of proline metabolism may be involved in the progress of gyrate atrophy.

Cholera toxin enhances taurine uptake in cultures of human retinal pigment epithelial cells.

Taurine uptake into cultures of human retinal pigment epithelial (HRPE) cells was monitored for 7 days after seeding. A culture medium containing 16% fetal bovine serum (FBS) was used for 2 days and switched to one with 8% FBS. Uptake of taurine (25 nM) was approximately 1.5 pmol/mg protein/15 min for 3 days, then decreased by 45% and was maintained at a decreased level till the 7th day. When the 16% FBS medium was used for the entire culture period, a similar profile of taurine uptake was observed but decrease of the uptake started on the 3rd day. Treatment of cells with 100 ng/ml cholera toxin (CT) for 24 h between the 6th and 7th days returned taurine uptake to its high level observed at the beginning of the cell culture. A similar CT treatment of cells between the 2nd and 3rd days enhanced taurine uptake significantly but this enhancement was much smaller. CT increased taurine uptake in treatment-time and dose dependent manners. Forskolin (FSK) (10 mM) and 8-Bromocyclic adenosine 3',5'-monophosphate (1 mM) also increased taurine uptake. KT5720 at 1 microM, a selective inhibitor of cAMP-dependent protein kinase (PKA), partially blocked CT-induced enhancement of taurine uptake. The level of cAMP was higher on the 3rd day than the 7th day but its response to 3-isobutyl-1-methyl-xanthine, FSK and CT was similar on both days. A kinetic analysis revealed that CT treatment decreases the apparent Michaelis-Menten constant of the taurine transporter while the drastic reduction of taurine uptake during the cell culture period is due to a decrease in the maximal velocity. The results show that cAMP elevated by CT treatment enhances taurine uptake via an increase in the affinity of the transporter. The decrease of taurine uptake during the culture period seems to be related to a decrease in the amount of the transporter.

Choroidal neovascular membrane associated with optic nerve head drusen in a child.

PURPOSE: To illustrate the diagnosis, evaluation, and complications of pseudopapilledema in children. METHODS: We examined a 9-year-old boy who had suspected papilledema and a retinal mass. He had undergone neuroradiologic imaging at an outside facility. RESULTS: Clinical examination of the patient provided the diagnosis of optic nerve head drusen, pseudopapilledema, and a cicatrized choroidal neovascular membrane. Examination of the boy's parents disclosed optic nerve head drusen in the father. CONCLUSIONS: Choroidal neovascular membranes caused by optic nerve head drusen are uncommon in children. Clinical examination of the patient and family members, along with B-scan ultrasonography, can establish this cause. Neuroradiologic testing is unnecessary, and carries risk related to the need for sedation.

Fat adherence syndrome treated with intraoperative mitomycin-C: a rabbit model.

We used an animal model of restrictive strabismus analogous to the fat adherence syndrome in humans to test the efficacy of topical intraoperative mitomycin-C (MMC) in preventing the development of restrictive scar tissue. A cicatricial adhesion was created between the inferior rectus muscle and the inferior orbital rim of each eye in eight rabbits, and passive forced ductions were quantitatively measured with a spring scale. Eight eyes were treated intraoperatively with topical MMC 0.5 mg/mL, the other eight with sterile water. Passive forced ductions were again measured 4 weeks postoperatively and representative orbits were exenterated for histopathologic examination. Significant restriction of motility was produced in six of the eight control eyes. Though prophylactic treatment with MMC may have been beneficial in some cases, on average, the restriction developing in these eyes did not significantly differ from that in the control eyes. In addition, longer exposure times to MMC led to marked orbital inflammation and severe restriction of ocular motility. Finally, histopathologic evaluation of the orbits of the MMC-treated eyes revealed marked fibrosis of perimuscular connective tissues. Although MMC may have a role in the management of fat adherence syndrome, further study is needed to establish safe and efficacious methods of delivery.

Establishment and maintenance of in vitro cultures of human retinal pigment epithelium.

The retinal pigment epithelium (RPE) is a layer of multipotential cells of neural ectoderm origin lying between Bruch's membrane and the neural retina. The RPE subserves several essential ocular functions, including phagocytosis of shed photoreceptor outer segments, maintenance of the blood-retinal barrier, absorption of stray light, regulation of the biochemical, metabolic, and ionic composition of the subretinal space, and induction of embryonic differentiation of adjacent neural retina and choroid (1). Experimental evidence indicates that early in embryonic life, the neural retina can regenerate from the pigment epithelium (2). In vitro cultures of pure RPE provide a vehicle for studying RPE function in both normal and diseased states, and may also serve as a model for other neural cells (3, 4). Multiple techniques have been described for culturing human RPE (5-12). The authors describe here a modtfication of the technique of Del Monte and Maumenee (10), which is simple and effective in establishing primary cultures and extended cell lines of human RPE for research.

Cyclic AMP-dependent up-regulation of the taurine transporter in a human retinal pigment epithelial cell line.

This investigation was undertaken to study the role of cAMP in the regulation of the taurine transporter expressed in a human retinal pigment epithelial (HRPE) cell line. Treatment of the HRPE cells with cholera toxin for 24 h was found to stimulate the taurine transporter activity, as measured by taurine transport into the cells in the presence of NaCl, to a significant extent. The stimulation was 50-60% at 100 ng/ml cholera toxin. This stimulation was specific to the taurine transporter since the transport of two other amino acids (leucine and alanine), which are not substrates for the taurine transporter, was not affected by cholera toxin under similar conditions. Exposure of the cells to cholera toxin for a time period > 4 h was needed to elicit the stimulatory effect. The cholera toxin-induced stimulation of the taurine transporter activity was associated with an increase in the maximal velocity of the transport system. The affinity of the transporter for taurine was not altered by the treatment. The stimulatory effect was markedly blunted when the treatment of the cells with cholera toxin was done in the presence of actinomycin D, an inhibitor of transcription, or cycloheximide, an inhibitor of translation. The increase in the taurine transporter activity induced by cholera toxin was associated with a 2.6-fold increase in the steady state levels of the transporter mRNA. Measurement of cyclic nucleotides in control and cholera toxin-treated cells revealed that the toxin caused a 20-fold increase in the cellular levels of cAMP, the levels of cGMP remaining unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Vertical shift of the medial rectus muscles in the treatment of A-pattern esotropia: analysis of outcome.

A retrospective study was performed on 18 consecutive patients with A-pattern esotropia and no apparent oblique muscle dysfunction, mechanical restriction, paresis, or previous muscle surgery. All patients underwent graded bilateral medial rectus recession for their esotropia with simultaneous vertical upshift to treat the A-pattern. The quantitative relationship between amount of upshift, amount of A-pattern correction, preoperative A-pattern, and preoperative esotropia was examined. We found that the amount of A-pattern correction was closely correlated with the size of the A-pattern preoperatively (r = 0.83), independent of amount of upshift. While the change in A-pattern did correlate with the amount of the upshift (r = 0.60), it was not a significant independent predictor of the surgical response. The amount of recession had little influence on the effectiveness of the procedure in correcting the vertical incomitance, and the transposition did not seem to affect the correction of the basic esotropia, adversely. We conclude that medial rectus recession with vertical upshift of the muscle insertions is an effective procedure for correcting the vertical incomitance in A-pattern esotropia, and that the amount of A-pattern correction achieved is determined primarily by the size of the preoperative A-pattern and not the amount of upshift.

Na(+)-dependent glutamate transporter in human retinal pigment epithelial cells.

PURPOSE: To characterize glutamate uptake in the human retinal pigment epithelial (HRPE) cell line 165 and to determine the feasibility of using this cell line as an experimental model for glutamate transport studies. METHODS: Confluent monolayers of the HRPE cells cultured in 35-mm petri dishes were used to study glutamate uptake with regard to its ion dependence, substrate specificity, and kinetics. The radioactivity associated with the cells was measured by a liquid scintillation counter. RESULTS: Glutamate uptake was noticeably stimulated by the presence of Na+ in uptake buffer. Acidic amino acids (100 microM; L-glutamate, L-aspartate, D-aspartate, and L-cysteate) and glutamate transporter inhibitors (100 microM; dihydrokainic acid, DL-threo-beta- hydroxyaspartic acid, and L-trans-pyrrolidine-2,4-dicarboxlic acid) interacted with uptake of radiolabeled glutamate. The activity of glutamate uptake depends on Na+ concentration. Glutamate uptake in the presence of Na+ does not have anion dependence. The uptake of glutamate was enhanced by external acidic environment and inhibited by 0.5 mM DIDS: Glutamate receptor antagonists (100 microM; [+/-]-2-amino-4-phosphonobutyric acid and 6-cyano-7- nitroquinoxaline-2,3-dione) did not inhibit glutamate uptake. Kinetic analysis shows that this transporter consists of at least two saturable systems. CONCLUSIONS: The results of the present study demonstrate that a glutamate transporter is expressed in the HRPE cells. Its characteristics are similar to those of glutamate transporters observed in the RPE of laboratory animals. The human cell line 165 will be a useful tool for characterization of glutamate transport in the RPE. This study also provides clear evidence for the presence of a glutamate transporter in the human RPE.

Molecular identity and calmodulin-mediated regulation of the taurine transporter in a human retinal pigment epithelial cell line.

The molecular identity and calmodulin-mediated regulation of the taurine transporter were investigated in a human retinal pigment epithelial cell line (HRPE). Reverse transcription-polymerase chain reaction amplification of HRPE cell mRNA using primer specific for a taurine transporter cloned from human placenta yielded a product of expected size (approximately 0.9 kb) which hybridized to the placental cDNA probe under high stringency conditions. The nucleotide sequence of the product was identical to the sequence of the portion of the placental taurine transporter cDNA flanked by the specific primers. The taurine transporter expressed in the HRPE cell line thus appears to be identical to the transporter cloned from the placenta. Treatment of the HRPE cells with a selective calmodulin antagonist CGS 9343 B (CGS) led to a marked decrease in taurine transport activity. This effect could be reproduced with W-7, another calmodulin antagonist. The inhibition caused by CGS occurred rapidly (t1/2 approximately 10 min). Treatment of the cells with CGS did not affect the transport of leucine, and amino acid not recognized by the taurine transporter as a substrate. The CGS-induced inhibition of taurine transport was accompanied by a decrease in the maximal velocity of the transporter with no detectable change in the substrate affinity. The steady state levels of the transporter mRNA however remained unaffected by CGS treatment. It is concluded that the HRPE cell line expressed a taurine transporter identical to the transporter describe in the human placenta and that the function of this transporter is regulated by calmodulin-dependent processes.

Properties of taurine transport in a human retinal pigment epithelial cell line.

The characteristics of taurine transport were studied in a human retinal pigment epithelial cell line (HRPE). Uptake of taurine into monolayer cultures of the HRPE cells was markedly stimulated by the presence of NaCl in the uptake medium whereas the uptake was negligible in its absence. This NaCl-dependent uptake was an active process as the cells were able to accumulate taurine against a concentration gradient. The uptake rate of taurine was found to be many-fold greater than that of gamma-aminobutyric acid (GABA). Unlabeled taurine and GABA competed with radiolabeled taurine for the uptake process, the former being more effective than the latter. However, uptake of radiolabeled GABA was not affected by unlabeled taurine and GABA. Substrate specificity studies revealed strong interaction of beta-amino acids with the transport system responsible for taurine uptake. alpha-Amino acids failed to inhibit taurine uptake. A specific anion requirement was observed for optimal activity of the taurine transport system and Cl- was the most supportive among several anions tested. Kinetic analyses showed that multiple Na+ and one Cl- were involved in transfer of one taurine molecule. The transport process consisted of a single saturable system with a Michaelis-Menten constant of 2.0 +/- 0.1 microM. These results show that the HRPE cell line expresses a high-affinity taurine transport system. This is the first demonstration of the presence of the taurine transporter in the human retinal pigment epithelium and the HRPE cell line may provide a useful model system for future studies involving taurine transport in the retinal pigment epithelium.

Inhibition of phosphatidylinositol synthase by glucose in human retinal pigment epithelial cells.

A series of interrelated biochemical and functional defects, induced by hyperglycemia, associated with intracellular depletion of D-myo-inositol, and corrected by aldose reductase inhibitors, have been ascribed to abnormal phosphoinositide metabolism in several tissues prone to diabetic complications. However, reductions in tissue D-myo-inositol content are not universally found in complications-prone diabetic tissues, and direct mass-action effects of cellular D-myo-inositol depletion on the critical CDPdiacylglycerol-inositol 3-phosphatidyltransferase (PI synthase; EC 2.7.8.11) step have never been shown conclusively in relevant cells. The studies reported here simultaneously estimated the chemical mass of CDP diglyceride by equilibrium labeling with 5-[3H]cytidine and phosphoinositide biosynthesis by the incorporation of [32P]orthophosphate into phosphoinositide. This was done to assess the degree of inhibition of PI synthase under various degrees of D-myo-inositol depletion and sorbitol accumulation induced by glucose and other metabolic manipulations in cultured human retinal pigment epithelial cells, a new in vitro model for diabetic complications. The results suggest that sorbitol accumulation limits the PI synthase reaction in these cells by selectively depleting specific intracellular pools of D-myo-inositol and/or by possible independent effects of sorbitol on PI synthase.

Sorbitol, myo-inositol, and rod outer segment phagocytosis in cultured hRPE cells exposed to glucose. In vitro model of myo-inositol depletion hypothesis of diabetic complications.

The "myo-inositol depletion hypothesis" remains a leading but still controversial contender among proposed pathogenetic mechanisms for the chronic complications of diabetes. The multifaceted interrelationships among altered tissue myo-inositol content and metabolism and tissue function have been difficult to elucidate in diabetic animal models due in part to the complex, heterogeneous nature of tissues prone to diabetic complications. The retinal pigment epithelium consists of a homogenous cell monolayer that exhibits related alterations in myo-inositol metabolism and function in diabetic animals. Nontransformed human retinal pigment epithelial (hRPE) cells, which retain their general phenotypic and morphological characteristics during monolayer culture in vitro, were examined for parallel alterations in myoinositol metabolism and cell function when grown under carefully controlled conditions in medium containing hyperglycemic concentrations of glucose. Exposure of hRPE cells to 20-40 mM glucose produced time- and dose-dependent increases in sorbitol content and decreases in myo-inositol content that were partially blocked by the aldose reductase inhibitor sorbinil. myo-Inositol was taken up by two Na-dependent transport systems, at least one of which was competitively inhibited by glucose. Exposure to 20 mM glucose impaired the ability of hRPE cells to take up human retinal rod outer segments, an important physiological function of these cells. The impairment of rod outer segment uptake by high glucose levels was prevented by an aldose reductase inhibitor or elevated medium myo-inositol that corrected the fall in myo-inositol content. Thus, hRPE cells provide a new in vitro model in which to examine the biochemical-functional interrelationships of the myo-inositol depletion hypothesis.

Monocyte chemotactic protein gene expression by cytokine-treated human retinal pigment epithelial cells.

Inflammation involving the retina and choroid is a common clinical problem, but the mechanisms that elicit and maintain ocular inflammation remain poorly understood. Interposed between the sensory retina and the systemic blood circulation within the choroid is the neural-derived retinal pigment epithelium (RPE), which forms part of the blood-retina barrier. The RPE is actively phagocytic and shares several features with mononuclear phagocytes of bone marrow origin, including the production of a neutrophil chemotactic factor, interleukin 8, after stimulation with interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF-alpha). Because monocyte-derived macrophages are present in retinal lesions of many common and blinding diseases, we monitored human RPE cells or monocyte chemotactic protein (MCP) mRNA expression and activity following cytokine stimulation. Cultured human RPE cells were left unstimulated or exposed to recombinant human IL-1 beta, TNF-alpha, or lipopolysaccharide. MCP mRNA expression in RPE cells and biologically active MCP in RPE cell supernatants were present 1 hour after stimulation and maintained for 24 hours. Conditioned media from RPE cells stimulated with 20 ng/ml of IL-1 beta or TNF-alpha for 24 hours contained biologically active monocyte chemotactic activity that rose rapidly from baseline levels over 4 hours and plateaued over the subsequent 20 hours. RPE chemotactic activity was dose dependent using concentrations of these cytokines ranging from 20 pg/ml to 20 ng/ml of 4-hour assays. Time- and concentration-dependent expression of RPE cell MCP mRNA was also found in the same cultures. Peak MCP mRNA expression occurred after 8 hours of stimulation with IL-1 beta or TNF-alpha. Maximal steady-state MCP mRNA expression occurred at 20 ng/ml for IL-1 beta. Immunohistochemical staining using specific anti-MCP antibodies resulted in distinctive RPE cell staining, confirming the presence of MCP in human RPE cells. These findings demonstrate that cytokine-stimulated RPE cells may evoke or augment mononuclear phagocyte-mediated ocular inflammation by synthesizing MCP.

Glycosaminoglycan degradation by cultured retinal pigment epithelium from patients with retinitis pigmentosa.

Patients with certain systemic deficiencies in the degradation of glycosaminoglycans (GAGs) often suffer from a retinal degeneration similar to that seen in retinitis pigmentosa. This applies to mucopolysaccharidosis (MPS) types I, II, and III, but not to type VI. The retinal pigment epithelium (RPE) is thought to contribute significantly to the synthesis and degradation of proteoglycans in the interphotoreceptor matrix. This raises the possibility that a defect in the synthesis or degradation of GAGs by the RPE may be related to some forms of retinal degeneration. In the present work, RPE from normal and RP donors was investigated for the capacity to correct deficiencies in GAG degradation by cultured skin fibroblasts from patients with different forms of MPS. A cross-correction technique was used in which abnormal increases in the incorporation of 35S-sulfate into GAGs by MPS fibroblasts was measured in the absence or presence of RPE cultures. RPE from normal donors corrected the defects in GAG degradation of fibroblasts from patients with MPS I, II, and III, but not MPS VI. The RPE from four donors with retinitis pigmentosa (one autosomal dominant, one sex-linked, and two isolated cases) and one donor with an unclassified isolated retinal degeneration demonstrated the same capacities to correct the MPS deficiencies as did normal RPE. Therefore, although retinitis pigmentosa is a heterogeneous disorder with several possible etiologies, no evidence was found in these five patients for a defect in GAG degradation that resembles the deficiencies of MPS patients.

Denervation and extirpation of the inferior oblique. An improved weakening procedure for marked overaction.

Parks demonstrated that recession was more effective than myectomy at insertion or origin, or disinsertion for eliminating inferior oblique overaction. This study simultaneously compares an improved procedure, an extirpation of the inferior oblique that involves denervating it, to 14 mm recession in a prospective, consecutive series of 16 patients with symmetrical 4+ overaction of the inferior obliques; one technique (extirpation) performed on the right eye, and the other (14 mm recession) on the left. Mean duration of follow-up was 20.8 months (range 17 to 34 months). Extirpation resulted in 100% normal action, without residual overaction or underaction. Recession, however, resulted in 1+ to 3+ residual overaction in 12 cases (75%) and 4+ overaction requiring reoperation in two eyes (13%). It appears that extirpation of the inferior oblique is far superior to 14 mm recession for treatment of marked overaction of the inferior oblique.

Histopathology of Sanfilippo's syndrome.

A 19-year-old woman with Sanfilippo's syndrome had poor vision, a flat electroretinographic pattern, and fundus changes similar to those in retinitis pigmentosa. Histology of her eyes by phase-contrast and electron microscopy showed extensive intracellular accumulation of fibrillogranular and membranous lamellar vacuoles in cornea, trabecular meshwork, iris, lens, ciliary body, and sclera. Retinal ganglion cells, retinal pigment epithelium (RPE), and optic nerve glia were similarly involved. Retinal pigment epithelial hyperplasia and hypopigmentation, intraretinal RPE migration, vascular attenuation, and marked photoreceptor loss were notable and closely resembled that occurring in inherited retinitis pigmentosa. We assume that the patient's blindness was due to photoreceptor cell loss, since the ganglion cells and optic nerve seemed to be intact. Although the cause of photoreceptor loss is unclear, the massive storage of acid mucopolysaccharide and lipofuscin within the RPE might disturb its essential metabolic functions and lead to photoreceptor degeneration.