Elevated vitreous interleukin-10 level is not diagnostic of intraocular-central nervous system lymphoma

OBJECTIVE: Diagnosis of intraocular-central nervous system (CNS) lymphoma is commonly made by identifying malignant lymphocytes in the vitreous. However, such cells are in the minority in the vitreous cellular infiltrate (most are reactive lymphocytes), and therefore lack of cytologic support from biopsied vitreous samples in patients suspected of having intraocular-CNS lymphoma may occur. Recent data suggest that interleukin-10 (IL-10) levels are elevated in the serum and vitreous of patients with non-Hodgkin's lymphoma, whereas IL-12 and IL-6 levels are elevated in patients with uveitis of non-neoplastic etiology. The authors evaluated the usefulness of measuring vitreous levels of IL-6, -10, and -12 in the diagnosis of intraocular-CNS lymphoma. DESIGN: Prospective case series. PARTICIPANTS: Seventeen patients with intraocular inflammation who underwent a diagnostic or therapeutic vitrectomy: 4 patients with intraocular-CNS lymphoma and 13 patients with uveitis unrelated to a neoplasm. INTERVENTION: Eighteen vitreous specimens were obtained prospectively. Concentrations of IL-6, -10, and -12 were measured by enzyme immunosorbent assay, and relative ratios of the interleukins were calculated. Cytopathologic examination and flow cytometry of vitreous cells were also performed. MAIN OUTCOME MEASURES: The ratio of IL-10/IL-12 and IL-10/IL-6 was calculated to assess any association of intraocular-CNS lymphoma and high vitreous IL-10 relative to IL-6 and IL-12 levels. RESULTS: The IL-10/IL-6 and IL-10/IL-12 ratio was greater than 1 in 8 of 14 vitreous specimens obtained from 13 patients with non-neoplastic uveitis. One of the four specimens from patients with cytologically proven intraocular-CNS lymphoma had vitreous IL-10/IL-6 and IL-10/IL-12 ratios of less than 1. CONCLUSION: Although a helpful diagnostic tool, an elevated vitreous IL-10 to IL-6 or IL-12 ratio is not always associated with intraocular-CNS lymphoma.     

Ocular Whipple’s disease: Earlier definitive diagnosis

PURPOSE: Whipple's disease is a rare, chronic, and multiorgan bacterial disease that predominantly involves the gut and its lymphatic drainage in middle-aged Caucasian men but may involve the eye. It is often difficult to diagnose and treat. We report results of one more polymerase chain reaction (PCR) analysis-diagnosed ocular Whipple's disease (OWD) case and the care of three new patients with ocular inflammation caused by OWD. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Three patients. METHODS: Diagnostic PCR was performed on a vitreous sample, medical records of three patients with OWD were reviewed, and a literature review (1907 to present) located 74 OWD cases. Analysis of published OWD cases to seek out factors that contribute to earlier, definitive diagnosis and treatment of OWD is made. MAIN OUTCOME MEASURES: Response of ocular inflammation and vision to treatment. RESULTS: One of 3 new and 4 of 74 published OWD cases reviewed were diagnosed with PCR on vitreous samples and subsequently successfully treated with antibiotics without devastating central nervous system (CNS) sequelae. CONCLUSION: Diagnostic PCR on vitreous samples and recognition of key presenting symptoms in patients with OWD allows earlier definitive diagnosis, when the disease may be more amenable to antibiotic treatment, compared with "late" CNS Whipple's disease in the cases reviewed.     

Intravenous immunoglobulin therapy for ocular cicatricial pemphigoid: a preliminary study

OBJECTIVE: To report the effects of intravenous immunoglobulin treatment of ten patients with progressive ocular cicatricial pemphigoid who did not respond to conventional immunomodulatory regimens. DESIGN: Noncomparative, interventional case series. PARTICIPANTS: Ten patients with biopsy-proven progressive cicatricial pemphigoid affecting the eyes who did not respond adequately to other local and systemic immunosuppressive treatment regimens. INTERVENTION: Intravenous infusions of pooled human immunoglobulin, 2 to 3 g/kg body weight/cycle, divided over 3 days, and repeated every 2 to 6 weeks. MAIN OUTCOME MEASURES: Reduction in conjunctival inflammation, prevention of progression of subepithelial conjunctival fibrosis, improvement in ocular symptoms (discomfort, photophobia), improved visual acuity, reduction in extraocular mucosal lesions. RESULTS: Clinical deterioration was arrested and resolution of chronic conjunctivitis was documented in all ten patients. Maximum therapeutic effect was observed and maintained after a minimum of 4 cycles of therapy; three patients required 12 cycles before disease control. The duration of therapy in these ten patients has been 16 to 23 months (mean, 19.3 months) with no treatment-induced side effects. Extraocular mucosal lesion resolution has occurred in all but one patient, Visual acuity has stabilized or improved in all ten patients, and subjective complaints of discomfort and photophobia have decreased in all patients. CONCLUSIONS: Intravenous immunoglobulin immunomodulatory therapy can be a safe and effective therapy for otherwise treatment-resistant ocular cicatricial pemphigoid.     

Orbital Disease: Examination and Diagnostic Evaluation

To properly treat orbital disease, it is necessary to establish an accurate diagnosis and to understand the biologic characteristics of the disorder.A systematic method of evaluating patients with exophthalmos and other orbital abnormalities is presented. The most common orbital lesions among adults and children are listed. Abnormalities which mimic exophthalmos and cause pseudoexophthalmos are described.Important features of the history and physical examination of patients with orbital diseases are given. A comprehensive outline is described for the evaluation of patients who may have ophthalmic Graves' disease. A logical sequence is presented in which initial orbital studies (roentgenograms, ultrasonography, and computed tomography) and secondary orbital studies (radionuclide scans, venography, and arteriography) should be performed. Examples are given of three-dimensional computed tomography, using both axial and coronal scans. Finally, special diagnostic studies that can be performed upon excised tissue (electron microscopy, cell surface immunology, hormone receptor assay, and tissue culture) are discussed.     

Do Eye Hospitals Have a Role in Our Future?

Eye hospitals, originally founded to care for the poor, have developed into academic centers and tertiary "hospitals of last resort." Inexorable economic pressures, especially price competition, are likely to close many of them, particularly those which are marginal in quality or management. Survival of the remainder may further depend on their ability to adapt to a rapidly changing environment and to fulfill, better than anyone else, the special mission of basic and clinical research and training. Society must be convinced that some of these complex, highly differentiated, relatively expensive eye hospitals are significant national resources, serve the public welfare, and are worth preserving.     

Late diagnosis of choroidal malignant melanomas in eyes with clear media and low visual acuity

Five patients seen in a one-year period with advanced malignant melanoma of the choroid in eyes with low visual acuity and clear media are reported. The low visual acuity appeared clinically to be antecedent to the malignant tumor; although in certain cases it may have been related to the occult melanoma, this was not appreciated clinically. Because of the low visual acuity, these patients did not have vision symptoms referable to the melanoma, and the malignancy was diagnosed late in its course. All five cases had extrascleral extension of the tumor at the time of surgical treatment; three are dead of metastatic disease, and two have undergone orbital exenteration with only brief follow-up periods. This experience suggests that eyes with clear media and low vision owing to presumably unrelated causes should undergo periodic examination to rule out the presence of a growing malignant melanoma and to prevent its late diagnosis.     

Ocular abnormalities occurring with vitiligo

One hundred twelve patients with vitiligo were examined for ocular abnormalities. Discrete areas of depigmentation with associated pigment hyperplasia clinically appearing to involve the choroid and retinal pigment epithelium were observed in 44 patients, and active uveitis was seen in nine patients. The changes observed suggest that the spectrum of diseases that includes Harada's disease and the Vogt-Koyanagi syndrome may be broader than previously appreciated. Patients with these syndromes may represent the most severe examples of vitiligo and uveal inflammation. The occurrence of symptoms of night blindness in 12 patients and a family history of retinitis pigmentosa in two of these may signify a possible malfunction of the retinal pigment epithelium. Further evidence for a pigment epithelium disorder is suggested by the high incidence of an unusually prominent choroidal pattern in these patients.     

New findings in the chromosome 13 long-arm deletion syndrome and retinoblastoma.

New clinical and pathologic findings in patients with deletion of the long arm of chromosome 13 (13q-) include optic nerve hypoplasia and retinal dysplasia. Fibroblasts derived from patients with a 13q- syndrome with and without retinoblastoma, as well as from familial and sporadic retinoblastoma, are a useful model for the study of genetic susceptibility to the development of spontaneous and radiation-induced cancers. Fibroblasts from patients with hereditary retinoblastoma appear more radiosensitive than fibroblasts from patients with sporadic retinoblastoma or normal control patients.     

Ophthalmic plastic applications of acellular dermal allografts

PURPOSE: Clinical problems of contracted conjunctival fornices, superior sulcus defects, and soft tissue contour defects in the periorbital region have not shown good, sustained results with a range of autologous and alloplastic implants. AlloDerm (Lifecell Corp., Woodlands, TX) is an acellular dermal graft processed from human donor tissue. The authors sought to assess the efficacy of AlloDerm as a soft tissue replacement in a variety of oculoplastic applications. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-three patients. METHODS: Applications were broadly classified as barrier/scaffolding (i.e., primary and secondary implant coverage, lid spacer graft) and volume augmentation (i.e., superior sulcus and other periorbital soft tissue contour defects). Barrier grafts were applied as single sheets. Stacked sheets or rolled grafts were used for augmentation. Collectively, this material was used in 29 cases with 3 to 16 months' follow-up. MAIN OUTCOME MEASURES: Clinical evaluation of outcome and complications. RESULTS: As a soft tissue scaffolding and barrier implant, AlloDerm persisted sufficiently to permit repopulation with native tissue. Rolled/stacked implants demonstrated unpredictable resorption. Upper eyelid grafts seemed to have higher resorption rates than lower eyelid grafts. One case of anophthalmic superior sulcus augmentation required two revision surgeries to provide sufficient volume augmentation. The grafts were well tolerated, with no cases of infection or explanation. CONCLUSION: Acellular human dermis is an excellent barrier and reconstructive grafting material that provides an alternative to autologous grafts and other alloplastic material, avoids harvesting autologous tissue, possesses excellent handling properties, and is associated with minimal inflammation. Long-term follow-up is required to evaluate persistence.     

Velocity and acceleration statistics of pseudorandomly timed saccades in humans

A system is described for the recording and analysis of the angular velocities and accelerations associated with 20° horizontal saccades. The acceleration data are included in order to bring out details of the velocity waveforms which otherwise might be ignored. The saccades are induced by a target system which operates on a pseudorandom time base, so that the timing of the saccades is not predictable. Statistical results for average peak velocities and accelerations of each eye are given for a group of 40 normal subjects. In addition an analysis is presented of the differences of pairs of individual velocities and accelerations, to provide additional statistical data which emphasize the interrelationships of these dynamic parameters of the two eyes. The significance and possible application of these sets of normative data are discussed.     

Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey.

OBJECTIVE: This study evaluated the effect of repeated photodynamic therapy (PDT) applications on normal primate retina and choroid using an intravenous infusion of liposomal benzoporphyrin derivative (verteporfin). DESIGN: This was an experimental study in a primate model. ANIMALS/CONTROLS: Six cynomolgus monkeys were used as experimental subjects and one monkey was used as a control subject. INTERVENTION: Three consecutive PDT treatments at 2-week intervals were applied over the center of the fovea or the optic nerve of each eye. Verteporfin was delivered by intravenous infusion at a dose of 6 mg/m2, 12 mg/m2, or 18 mg/m2. Laser irradiation was then applied using a diode laser (689 nm) with light doses and spot sizes kept constant. MAIN OUTCOME MEASURES: Findings were documented by fundus photography, fluorescein angiography, and light and electron microscopy. RESULTS: A cumulative dose response was seen angiographically and histologically with more severe damage to the retina and choroid noted at higher dye doses. Photodynamic therapy applied to the macula using the 6-mg/m2 verteporfin dose showed recovery of choriocapillaris, with mild retinal pigment epithelium and outer photoreceptor damage at 6 weeks. At this dose, the optic nerve showed few focal sites of axon atrophy and capillary loss. Treatments over the macula using the 12-mg/m2 and 18-mg/m2 doses led to chronic absence of choriocapillaris and photoreceptors at 6 weeks. One of two optic nerves became atrophic after PDT applications using dye doses of 12 mg/m2, and both optic nerves became atrophic in the 18-mg/m2 dye dose group. CONCLUSION: Limited damage to the retina, choroid, and optic nerve was present in primates treated with multiple PDT sessions using 6 mg/m2 verteporfin with light doses and the timing of irradiation kept constant. However, PDT using higher dye doses of 12 mg/m2 and 18 mg/m2 led to significant chronic damage to the normal retina, choroid, and optic nerve.     

Late traumatic dislocation of laser in situ keratomileusis corneal flaps

PURPOSE: To report the management and outcome of late-onset traumatic dislocation of laser in situ keratomileusis (LASIK) flaps. DESIGN: Retrospective, observational case series. PARTICIPANTS: Four patients with late-onset LASIK flap dislocation occurring after mechanical trauma at various intervals (10 days-2 months) after the procedure. INTERVENTION: In all cases of postoperative traumatic LASIK flap dislocation, the flap was refloated with scraping and irrigation of the underlying stromal bed within 12 hours of the injury. A bandage contact lens was placed, and a regimen including topical antibiotics and corticosteroids was instituted in all cases. MAIN OUTCOME MEASURES: Best spectacle-corrected visual acuity and complications associated with the surgery were monitored. RESULTS: Postoperative follow-up ranged from 4 to 21 months. Nonprogressive epithelial ingrowth was noted in one patient and diffuse lamellar keratitis developed in another patient. All patients recovered pretrauma spectacle-corrected visual acuity. CONCLUSIONS: Corneal LASIK flaps are prone to mechanical dislocation as late as 2 months after the procedure. Appropriate management results in recovery of optimal visual outcomes.     

Ocular Toxocariasis Presenting as Leukocoria in a Patient with Low ELISA Titer to Toxocara canis

A 4-year-old white female presented with leukocoria of the right eye. White punctate lesions were observed posterior to the retrolental membrane, which suggested retinoblastoma to some examiners. A full history, physical examination, ultrasonography, and CT scan failed to rule the diagnosis of retinoblastoma in or out. A serum ELISA titer was 1:4, which was considered nondiagnostic. Examination of the enucleated eye revealed a midsegment of the second stage larva of Toxocara canis. The strengths and weaknesses of various diagnostic modalities used to differentiate leukocoria caused by retinoblastoma and T canis are discussed.     

Assessment of mutations in the Best macular dystrophy (VMD2) gene in patients with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and bull's-eye maculopathy.

PURPOSE: To study the presence of Best macular dystrophy (VMD2) gene mutations in patients diagnosed with maculopathies other than classic Best disease and to describe the clinical characteristics of these subjects. DESIGN: Case-comparison study of phenotype-genotype correlations. METHODS: Patients with either age-related maculopathy (ARM; n = 259) or maculopathies other than classic Best disease (n = 28) were screened for mutations in the Best gene (VMD2; OMIM 153700). These cases were compared with ethnically similar subjects in the same age range without maculopathy (n = 196). All patients underwent a complete dilated ocular examination, and all affected individuals underwent fundus photography. Phenotype-genotype comparisons were made. MAIN OUTCOME MEASURES: Presence of mutations in the Best gene (VMD2; OMIM 153700) and the clinical phenotype. RESULTS: Three of 259 patients (1%) with ARM and 2 of 28 patients (7%) with other maculopathies including 1 of 3 patients with adult-onset foveomacular vitelliform dystrophy and 1 of 5 patients with a bull's eye maculopathy, but none of the controls, were found to possess amino acid-changing variants in the VMD2 gene. These included a man with confluent drusen and retinal pigment epithelial detachments (variant in exon 6; T216I), a man with geographic atrophy and numerous soft drusen (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations (variant in exon 10; L567F), a woman with drusen and retinal pigment epithelial alterations resembling bull's-eye maculopathy (variant in exon 4; E119Q), and a woman diagnosed with adult-onset foveomacular vitelliform dystrophy (variant in exon 4; A146K). CONCLUSIONS: Novel mutations in the VMD2 gene were found in patients diagnosed with maculopathies other than classic Best disease. Some cases diagnosed as adult-onset vitelliform foveomacular dystrophy may represent a variant of Best disease with delayed onset. The VMD2 gene does not play a major role in the development of ARM.