Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy.

The hereditary macular dystrophies are progressive degenerations of the central retina and contribute significantly to irreversible visual loss in developed countries. Among these disorders, Sorsby's fundus dystrophy (SFD), an autosomal dominant condition, provides an excellent mendelian model for the study of the genetically complex age-related macular degeneration (AMD), the most common maculopathy in the elderly. Recently, we mapped the SFD locus to 22q13-qter. This same region contains the gene for tissue inhibitor of metalloproteinases-3 (TIMP3), which is known to play a pivotal role in extracellular matrix remodeling. We have now identified point mutations in the TIMP3 gene in affected members of two SFD pedigrees. These mutations are predicted to disrupt the tertiary structure and thus the functional properties of the mature protein.

Retinitis Pigmentosa. A biomicroscopical study of vitreous abnormalities.

A biomicroscopical study of the vitreous body was performed on 116 eyes of 58 patients with primary retinitis pigmentosa, and six additional eyes were examined histopathologically. A characteristic vitreous degeneration, found in all eyes, was clinically divided into four sequential stages that appear to parallel the magnitude of gross retinal destruction as determined by visual-field measurements. The vitreous breakdown in retinitis pigmentosa may be due to progressive loss of hyaluronic acid from the hyaluronic acid-collagen complex.

The fishmouth phenomenon. I. Clinical characteristics and surgical options.

A typical fishmouth retinal break is a large horseshoe-shaped tear, located near the equator, with an associated bullous retinal detachment. During scleral buckling and drainage of subretinal fluid, the break tends to open more widely, making its closure difficult. Clinical characteristics that permit preoperative anticipation of the fishmouth phenomenon and several surgical methods that were previously suggested for its management are reviewed. The surgical methods include: an equatorial implant with a meridional addition, a two-band procedure, broad scleral buckling, and episcleral silicone sponge. A radial, intrascleral, solid-silicone implant (wedge) with an encircling element is recommended, as are other technical maneuvers that may be helpful in troublesome cases.

The fishmouth phenomenon. II. Wedge scleral buckling.

Radial retinal folding, associated with equatorial scleral buckling, contributes to the difficulty in repairing a retinal detachment due to a fishmouth break. To minimize this effect, a wedge-shaped implant was designed to approximate more closely the same relative reduction in the circumference of the circles of the globe along the meridian of the break. The surgical details of use of the implant are described. In a consecutive series of 56 eyes in which the fishmouth phenomenon was expected, 49 (88%) were successfully managed at first encounter using a wedge buckling device. Revised scleral bucklings and open-sky vitrectomies, in early failures and delayed recurrences, salvaged additional eyes for final success in 52 (93%) of the eyes.

The fundus in mongolism.

The fundus in 63 eyes of 32 karyotyped patients with mongolism (Down syndrome) was examined by indirect ophthalmoscopy. Common features included a rosy disc associated with a greater than normal number of retinal blood vessels, a generalized attenuation of fundus pigmentation regardless of iris coloration, peripapillary and patchy peripheral areas of pigment epithelial atrophy, and choroidal vascular "sclerosis." These findings are believed to be suggestive but not pathognomonic of mongolism. Eleven eyes of six additional patients were found to have retinal detachment. Eight of these were due to a retinal dialysis and only two could be surgically reattached. Trauma was thought to be an important predisposing factor. Several suggestions for prevention and early diagnosis of this complication are briefly presented.

Factors influencing retinal redetachment after removal of buckling elements.

Scleral buckling elements were removed from 152 eyes because of infection (50 eyes), erosion (69 eyes), extrusion (25 eyes), pain (5 eyes), allergy (2 eyes), and excessive buckle height (1 eye). The overall retinal redetachment rate was 14.5%. Short duration of buckling and the presence of retinal tears, as opposed to holes, appeared to predispose to recurrence. A significantly higher redetachment rate was found when infected buckling elements were considered alone (28%). This was attributed to the short duration of buckling and the associated inflammatory reaction found in these eyes.

Optic nerve pit and baring of the circumlinear vessel.

The concept of a circumlinear vessel (CLV) of the ophtic disc was recently introduced into the opthalmic literature, and baring of the CLV was suggested as a sign of acquired disc injury, especially from glaucoma. In a review of fundus photographs of 27 eyes with optic nerve pits, only one eye was found in which the CLV was bared. This observation supports the concept that baring of the CLV is a sign of acquired disc change.

Monochromatic ophthalmoscopy and fundus photography. The normal fundus.

Anatomical details in the ocular fundus can be seen with increased contrast when appropriate monochromatic illumination is used. This technique permits more accurate visualization and documentation than can be achieved with white light. This article reports the optimal spectral ranges for visualization of the different fundus structures. It describes and illustrates the appearance of individual structures and areas of the fundus under different spectral illuminations. There is a detailed discussion of the optical properties of the fundus layers that provides a background for interpreting the data and a baseline for examination of pathologic conditions.

Microhemorrhagic maculopathy.

Twenty subjects, 12 males and eight females aged 14 to 58 years, had a small monocular macular hemorrhage that was punctate, round, or bilobed and seemed to originate from the perifoveal capillary plexus. Although clinical study results failed to establish a common causal denominator, three of the 20 patients had a history of preceding increased venous pressure (Valsalva stress), three of nine subjects tested showed impaired blood platelet aggregation, and an additional four of 20 were taking medications known to impair platelet function both in vitro and in vivo. Macular microhemorrhages resolve spontaneously, and available data suggest that the syndrome is benign.

Hyaluronic acid vitreous substitute. A six-year clinical evaluation.

Hyaluronic acid vitreous substitute (HYVISC) was used during 347 operations performed on 294 eyes of 286 patients. It was injected intraocularly in 266 operations (73 scleral bucklings, 175 open-sky vitrectomies, among others) on eyes with complex retinal detachments that were considered inoperable by ordinary surgical techniques. During 81 closed vitrectomies, it was applied extraocularly between the surgical contact lens and the cornea. Hyaluronic acid was found to be well tolerated by human eyes. In eyes that had been given a poor prognosis, scleral buckling with hyaluronic acid tamponade produced reattachment in 16% of the eyes; open-sky vitrectomy, scleral buckling, and hyaluronic acid salvaged 18%. It also appeared helpful in the preservation of corneal epithelial integrity and clarity during closed vitrectomy.

Graphics composition of fundus data.

I developed a simple, inexpensive method of combining and recording clinical fundus data from a variety of sources in an instant color print or color transparency format. The system is useful for sequential observation, for planning laser treatment, for reference during photocoagulation, and for follow-up in many diseases including macular degeneration.

The pleomorphism and complications of posterior hyperplastic primary vitreous.

Among 30 patients examined, posterior hyperplastic primary vitreous was monocular in 25 and binocular in five. Poor vision and strabismus were the most common presenting complaints. All patients had vitreous membranes usually extending from the disk toward the equatorial zone. In 70% of the affected eyes, the vitreous membranes were associated with a radial retinal fold. Macular function was disturbed in 70% and retinal detachment was observed in 45% of the eyes. One extensive retinal detachment was successfully treated by scleral buckling; another detachment, limited to the posterior pole, responded to sectioning of a vitreous band with scissors.

Macular complications associated with posterior staphyloma.

PURPOSE: To report macular abnormalities associated with posterior staphyloma in eyes with myopia. METHODS: In a retrospective study, we surveyed 116 eyes of 58 patients with myopic refractions. Myopic fundus abnormalities are related to clinically quantified posterior staphyloma formation. RESULTS: A posterior staphyloma was present in 88 (75.9%) of 116 eyes with myopic refractions of -3 diopters or more. Best-corrected visual acuity was decreased among eyes in all staphyloma grades. Eyes with the shallowest staphyloma depth (grade 1) displayed the largest drop in visual acuity as well as the greatest frequency of choroidal neovascular membranes and hemorrhages. A linear relationship was observed between staphyloma grade and conus formation (P = .001), retinal pigment epithelial defects (P = .0001), lacquer cracks (P = .0001), and chorioretinal atrophy (P = .001). All these variables were increased in staphylomatous eyes. A significant difference in means by staphyloma grade was observed for myopic refractive error (P = .001), axial length (P = .001), and best-corrected visual acuity (logMAR, P = .0001). CONCLUSIONS: There was an unexpected high frequency of choroidal neovascular membranes, hemorrhage, and poor best-corrected visual acuity in the lower staphyloma categories. This suggests that the development of a choroidal neovascular membrane requires relative preservation of the choriocapillaris as present in eyes with less advanced stages of posterior staphyloma formation.

Prevalence of lattice degeneration and its relation to axial length in severe myopia.

We studied 436 eyes of 218 patients with myopia of -6.00 diopters or more in both eyes. Of 218 patients, 72 (33.0%) had lattice degeneration of the retina. Among these 72 patients, lattice lesions were uniocular in 39 (54.2%) and binocular in 33 (45.8%). Of 105 males, 33 (31.4%) had lattice degeneration; of 113 females, 39 (34.5%) had lattice degeneration. Contrary to previously published data, we found an inverse relationship between axial length and the prevalence of lattice degeneration in severely myopic eyes. The greatest prevalence of lattice degeneration (63 of 154 eyes, 40.9%) was found in eyes with an axial length of 26.0 to 26.9 mm (-6.00 to -8.70 diopters), and the least prevalence of lattice degeneration (five of 71 eyes, 7.0%) was found in eyes with an axial length of 32.0 mm (-24.00 diopters) or greater. This may explain the observation that retinal detachment after cataract surgery has been noted more commonly among patients with moderate than severe myopia.

Transient visual loss in ornithine transcarbamoylase deficiency.

We examined a 32-year-old, previously healthy man who developed episodic bilateral visual impairment and confusion. Coincident hyperammonemia led to the diagnosis of ornithine transcarbamoylase deficiency, which was established by enzymatic analysis of a liver biopsy specimen. The available data were insufficient to determine if the metabolic derangement impaired vision at the level of the optic nerves or at the cerebral level.

Hereditary hemorrhagic macular dystrophy.

We treated two brothers who had a hemorrhagic macular lesion in one eye; a similar problem affected the fellow eye of both patients within eight months. Generalized fine granularity of the retinal pigment epithelium and peripheral iris transillumination defects were observed in both siblings. A study of the family suggested that the disorder was dominantly inherited and probably was Sorsby's pseudoinflammatory macular dystrophy. The macular lesions in one brother were treated by argon green laser photocoagulation and in the other brother by krypton red laser photocoagulation. Although the brother treated by krypton red laser photocoagulation attained better final visual function, additional differences in treatment methods also may have contributed to the final outcome.

Myopic cracks, angioid streaks, and traumatic tears in Bruch's membrane.

We studied the pattern of break formation in 60 eyes with myopic lacquer cracks, angioid streaks, or traumatic tears in Bruch's membrane, using a graphics composition technique and computer analysis of digitized images. Lacquer cracks were found in a reticular distribution within a posterior staphyloma; angioid streaks occurred in a spider-web configuration centered on the optic nerve; traumatic tears were characteristically curved, perineural, and eccentric temporally. The specific break patterns imply the operation of biomechanical forces.

Transmission electron microscopic observations of vitreous abnormalities in retinitis pigmentosa.

Ultrastructural studies of six vitreous biopsy specimens obtained during cataract surgery on patients with retinitis pigmentosa showed four types of cells. These were ocular pigment epithelium, uveal melanocytes, retinal astrocytes, and macrophage-like cells. The fibrous astrocytes displayed plump cell bodies, large nuclei, and numerous intracytoplasmic filaments. The pigment epithelial cells and uveal melanocytes were round to cuboidal and were heavily pigmented. Macrophage-like cells demonstrated round cell bodies, inclusions of glycogen, and long processes extending from the cell membrane. Also identified in the vitreous material were loose pigment granules. In contrast, vitreous from the control group showed occasional macrophages and loose pigment. These findings explained the clinical observation of material within the vitreous of patients with retinitis pigmentosa.

Scleral buckling for retinal detachment in patients with retinoblastoma.

Three children (two girls and one boy) with bilateral retinoblastoma each developed a presumed rhegmatogenous retinal detachment in one eye. All three eyes had previously received radiation and cryotherapy. In each case the retinal detachment responded promptly to conventional surgical methods via scleral buckling in the area of treated retinoblastoma and presumed retinal break. All three eyes have retained useful vision for follow-up periods of 3.5 to 12 years.

Distinctive cataract in the Stickler syndrome.

We determined the clinical characteristics of cataract in 133 patients with the Stickler syndrome. Cataracts of various types or aphakia were found in 115 of 231 eyes (49.8%) studied. The most frequent and distinctive lesions, described as wedge and fleck cataracts, accounted for 40 of the 93 cataracts (43.0%) observed. These distinctive opacities may serve as a clinical marker for the Stickler syndrome and facilitate early diagnosis.