Cataracts after bone marrow transplantation: long-term follow-up of adults treated with fractionated total body irradiation.

PURPOSE: To determine the risk of, and risk factors for, developing cataracts after bone marrow transplantation. METHODS AND MATERIALS: Four hundred and ninety-two adults who underwent bone marrow transplantation in Seattle were followed for 2 to 18 (median, 6) years. Before transplantation, patients received a preparative regimen of chemotherapy plus total body irradiation (TBI) (n = 407) or chemotherapy alone, without TBI (n = 85). TBI was administered in a single dose of 10 Gy (n = 74) or in fractionated doses totaling 12-15.75 Gy (n = 333). The risk of cataracts was determined for groups of patients with respect to the type of preparative regimen received and other pretransplant and posttransplant variables. RESULTS: One hundred and fifty-nine patients (32%) developed cataracts between 0.5 to 11 (median, 2.3) years after transplantation. The probability of cataracts at 11 years after transplantation was 85%, 50%, 34%, and 19% for patients receiving 10 Gy of single-dose TBI, > 12 Gy fractionated TBI, 12 Gy fractionated TBI, and no TBI, respectively (p < 0.0001). Among those developing cataracts, the severity was greater in patients after single-dose TBI (59% probability of surgical extraction) than after > 12 Gy fractionated TBI, 12 Gy fractionated TBI, or no TBI (33%, 22% and 23%, respectively). Patients given corticosteroids after transplant had a higher probability of cataracts (45%) than those without steroids (38%) (p < 0.0001). In a proportional hazards regression model, the variables that were correlated with an increased probability of cataracts were single-dose TBI (relative risk (RR) = 2.46) and steroid therapy (RR = 2.34), while a decreased probability of cataracts was correlated with a nonTBI preparative regimen (RR = 0.41). The yearly hazard of developing cataracts in recipients of single-dose TBI was highest during the third year after transplantation, while in recipients of fractionated TBI, the hazard was distributed among years one through seven. The probability of cataracts in all groups reached a plateau at 7 years after transplantation, after which the development of cataracts was extremely unlikely. CONCLUSION: TBI is the major risk factor for developing cataracts after BMT. Single-dose TBI results in the highest risk of cataracts. However, the risk of cataracts in recipients of fractionated-TBI is significantly higher than in patients who receive no TBI. In addition to TBI, steroid therapy is an independent risk factor for cataracts after BMT.

Glaucoma. A general perspective.

Glaucoma is the most prevalent disease ophthalmologists deal with. It affects the elderly more commonly and has a higher incidence in blacks. This review covers basic precepts of the disease including tips to help the general physician identify suspect cases. Aspects of treatment, including surgical management, are considered, especially when these intersect with the general practice of medicine.

Color vision testing.

1. Color deficiency occurs in about 8% of the population, due to alterations in the chemistry of one of the three receptive pigments for colored light, or the substitution of one pigment for another in the photoreceptor cones. 2. Subjects with pigment alteration can see a broad range of color; those with substitution of one pigment for another have broad areas of color perception defect. 3. The most common tests are pseudoisochromatic (color confusion) plates, designed with patterns hidden to the color deficient. Other tests use colored caps, tracing patterns, or an anomaloscope.

Optic nerve head axonal transport in rabbits with hereditary glaucoma.

Rabbits with hereditary glaucoma develop ocular changes that resemble human congenital glaucoma and buphthalmia. The inheritance is autosomal recessive (bu). Previous research was performed primarily on albino bu/bu rabbits that were unhealthy and bred poorly. We have bred pigmented bu/bu rabbits to determine if this would improve hardiness and provide a better model for the disease in humans. First-generation offspring from matings of bu/bu albino with bu/bu pigmented rabbits were all affected, indicating that the bu gene is found at the same locus in both strains. The pigmented bu/bu offspring had a high degree of mortality, as reported previously for albino bu/bu rabbits. Newborn bu/bu rabbits initially had normal intraocular pressure (IOP; 15-23 mmHg); after 1- to 3 months, the IOP increased to 26-48 mmHg. The eyes became buphthalmic and the IOP returned to normal or sub-normal levels after 6-10 months. Since the lamina cribrosa is absent or poorly formed in the rabbit optic nerve head (ONH), this model was used to test the role of mechanical factors in the etiology of ONH pathology caused by increased IOP. Orthograde axonal transport was evaluated in both eyes from eight normal and 24 bu/bu rabbits of different ages, using intravitreal injections of [3H]leucine to mark orthograde axonal transport, followed by light- and electron-microscopic radioautography of the ONHs and superior colliculi. Normal rabbits of all ages showed no blockage of axonal transport in the ONH. All optic axons from young bu/bu rabbits with normal IOP and most axons from older buphthalmic rabbits that previously had elevated IOP were normal morphologically. Small zones of transport blockage occurred in bu/bu eyes while IOP was elevated; most affected axons lay immediately adjacent to ONH connective tissue beams that radiate outward from the central retinal vessels to the optic-nerve sheath. Thus, the rabbit, which lacks a true lamina cribrosa, does not show marked blockage of axonal transport as occurs in the LS of the monkey and cat ONH when IOP is elevated acutely. This anatomic difference appears to be protective against axonal damage, since bu/bu rabbits with chronic IOP elevation did not show significant loss of optic axons. These results are consistent with the proposed 'mechanical' theory of ONH damage resulting from increased IOP. Electron-microscopic radioautography revealed that chronically elevated IOP in bu/bu rabbits, which caused small foci of blocked ONH axonal transport against ONH beams, also caused degeneration of a few optic nerve terminals in the superior colliculi as the disease progressed.(ABSTRACT TRUNCATED AT 400 WORDS)

Breakdown of the outer blood-retinal barrier in experimental commotio retinae.

An animal model has been developed in this study to produce commotio retinae (Berlin's edema) by means of standardized, non-penetrating B.B. pistol injury to the cornea. Parameters have been established to ensure uniform blunt injury, enabling study of the retina and blood-retinal barrier by light- and electron microscopy, including use of horseradish peroxidase as a vascular tracer. Retinal whitening and swelling were found in the peripapillary and central regions, as occurs in the human. The earliest damage involved breakage of the connecting cilia of rods and cones, with rapid disorganization of the outer segments. Later changes included swelling of photoreceptor inner segments and breakdown of the outer blood-retinal barrier at the level of the retinal pigment epithelium. The outer blood-retinal barrier was re-established between 7 and 14 days, and at the longest survival (56 days), incompletely regenerated outer segments were present. This model for commotio retinae provides a new approach for the study of outer-segment regeneration in rods and cones after mechanical injury, as well as mechanisms that underlie re-establishment of the blood-retinal barrier following non-penetrating trauma to the eye.

Levobunolol. A three-month efficacy study in the treatment of glaucoma and ocular hypertension.

The ocular hypotensive effect and the safety of levobunolol hydrochloride (0.5% and 1%) were compared with vehicle in this double-masked study of 42 patients with chronic open-angle glaucoma or ocular hypertension. After a washout of ocular hypotensive medication, patients received one of the three test treatments in both eyes twice daily for three months. Both concentrations of levobunolol produced significant reductions in intraocular pressure, while decreases in vehicle-treated patients were minimal. Over the three-month study period, average pressure reductions were approximately 9.0 mm Hg in patients receiving either concentration of levobunolol and 0.5 mm Hg in patients receiving vehicle. Fewer patients were terminated from the study for inadequately controlled intraocular pressure in the levobunolol groups than in the vehicle group. No patients were terminated for drug-related adverse experiences.

Metaphors of glaucoma.

In a phenomenological study of glaucoma as an illness, 31 patients were interviewed. The goal of the study was an explication of the meanings of the experience of glaucoma, in a twofold sense: (1) the face, the role, or the self of the patient that responds to the illness; (2) the visage that the illness presents to the patient. This twofold explication was achieved by generating a classification of the interviews in terms of the dominant metaphor that emerged in each interview. The following basic metaphors are presented through case material: glaucoma as an accompaniment of aging, as blindness, as pressure, as an abstraction (and a weapon), and as fate. Variations on these themes demonstrate the necessity, in such work and for enhanced communication with patients, of paying attention to both the face that the illness presents and to the self that responds.

Thirty-year history of sympathetic ophthalmia.

A spontaneous corneal perforation followed by granulomatous uveitis occurred in a 10-month-old female infant with bilateral anterior segment anomalies. The histopathologic findings in the enucleated right eye and the 30-year course of intraocular inflammation in her left eye are consistent with sympathetic ophthalmia. This case illustrates that sympathetic ophthalmia can be overlooked for years unless the diagnosis is considered and periodic anterior segment biomicroscopy and indirect ophthalmoscopy are performed in patients who have had perforating ocular injuries. A lensectomy-vitrectomy procedure was successful in restoring ambulatory vision in this patient.

Bilateral subconjunctival hemorrhage after acetylsalicylic acid overdose.

Isolated bilateral subconjunctival hemorrhages developed in an adult patient after ingestion of a large amount (6.48 g) of aspirin. The time course and bilateral pattern suggest a direct metabolic relationship between these two events. Adverse ocular effect of aspirin previously described have not included this finding. Treatment was supportive for the ingestion and was accompanied by spontaneous clearing of the hemorrhage.

Resorbable implant for orbital defects.

Tricalcium phosphate ceramic, a synthetic bone substitute, was inserted into defects created in the inferior orbital rims of 18 rabbits. The animals were killed after three, eight, 24, and 40 weeks. Early sections demonstrated encapsulation with fibrous ingrowth. After eight weeks, osteoid formation was evident with partial resorption of the porous mineral implant. After 24 and 40 weeks, there was progressive replacement of tricalcium phosphate ceramic with trabecular bone, without signs of infection, migration, or rejection.

Bronchocentric granulomatosis with eye involvement.

Bronchocentric granulomatosis is a recently defined entity within the "pulmonary angitis and granulomatosis" group of lung diseases. Unlike the other granulomatoses, extrapulmonary disease has not been encountered with bronchocentric granulomatosis. Therefore, we report a case demonstrating apparent association with scleritis, an uncommon eye disorder often accompanying underlying systemic disease. This introduces a potential source of diagnostic confusion with Wegener's granulomatosis, which can resemble bronchocentric granulomatosis clinically and radiographically, and which has a known association with scleritis.

Alveolar soft-part sarcoma of the orbit.

An 11-month-old white female with a three-month history of swelling of soft tissue around the right eye presented with a proptotic globe and marked limitation of motility. A CT scan showed a soft-tissue mass in the orbit, which was biopsied and examined by light and electron microscopy. The specimen consisted of large polygonal and cuboidal cells of uniform appearance arranged in pseudo-alveoli around capillaries. The nuclei were pale and ovoid with prominent nucleoli and rare mitoses. The cytoplasm was packed with lipid droplets and the paranuclear region contained clusters of periodic acid-Schiff (PAS)-positive, diastase-resistant granules and needle-shaped crystals, which showed a linear periodicity of 100 nm by electron microscopy. These cytoplasmic crystals, which were diagnostic for alveolar soft-part sarcoma, were also found to be acid phosphatase-positive and, therefore, components of the lysosomal system. A lid-sparing exenteration of the right orbit was performed, and subsequent radiation therapy by cesium implant delivered 24,000 rads to the operative site. The patient is alive at 22 months following initial biopsy with no evidence of tumor recurrence.

Pilocarpine ocular inserts.

Pilocarpine was administered to a selected group of ocular hypertensive subjects in the form of a synthetic biosoluble matrix inserted into the conjunctival cul-de-sac. Satisfactory lowering of the intraocular pressure resulted, with a minimum of subject intolerance. The decreased pressure response was significant in some cases for greater than 24 hours. Drug delivery by soluble inserts offers promise as a convenient and effective mode of therapy.