J. Brooks Crawford

Histopathology of birdshot retinochoroidopathy

Birdshot retinochoroidopathy is a chronic posterior segment inflammatory disease with a characteristic clinical presentation and strong correlation with the HLA-A29 antigen.1,2 In this report, we describe the histopathological findings in the eye of a patient with this disease. A 49 year old white man was referred to the Proctor Medical Group in 1996 for evaluation of multifocal choroiditis (MFC). This had been an incidental finding on routine examination by his primary ophthalmologist. The patient was bothered by his refractive error, but denied problems with night or colour vision, and did not notice floaters. The patient’s past ocular history was notable for myopic correction since childhood. Radial keratotomy (RK) had been performed in both eyes in 1993, with subsequent fluctuations in his refraction. His past medical history was notable for a small cutaneous melanoma removed 5 months before presentation. He had been started on oral prednisone for his MFC before his referral to Proctor. Best corrected visual acuity was 20/20 in both eyes, and the intraocular pressures were 14 mm Hg. External examination was unremarkable, and the anterior segments showed RK scars and no inflammation. Trace vitreous cell was noted in both eyes. The optic nerve heads appeared pink and healthy, and the vasculature was unremarkable. Multiple cream-coloured round and oval spots were scattered throughout the posterior poles of both eyes, more prominent nasally (Figs 1A and B). The spots averaged approximately 500 μm in diameter, and were deep to the neural retina. The macula in each eye was flat with appropriate pigmentation. The fundus had a very “blond” appearance consistent with the patient’s complexion. Figure 1 Clinical and fluorescein angiographic (FA) findings. (A) Right …

Retinal Toxicity Secondary to intraocular Gentamicin Injection

The authors present five cases of severe retinal ischemia associated with gentamicin injection. In three of the cases massive doses of gentamicin were erroneously injected into the eye; in two of the cases the authors presume that gentamicin toxicity occurred. The sequence of clinical findings was similar in all five cases. The prominent findings included early superficial and intraretinal hemorrhages, opaque and edematous retina, cotton-wool infarcts, arteriolar narrowing, and venous beading. Fluorescein angiography revealed severe retinal vascular nonperfusion. Chronic findings included rubeosis irides, neovascular glaucoma, retinal pigmentary degeneration, and optic atrophy. Of the documented cases of massive intraocular gentamicin injection, two patients had no light perception (NLP) vision and one had bare light perception. Of the two cases of presumed gentamicin toxicity, one had 20/400 vision and one had count fingers vision. Strict precautions are necessary to prevent the catastrophic events resulting from inadvertent gentamicin injection; such precautions should include precise labeling of all injectable solutions on the surgical field, waiting to draw up injectable antibiotics until the time they are needed, and drawing up injectable antibiotics under direct physician observation. All intravitreal injections should be performed slowly, in the anterior vitreous, with the needle bevel up.

The pathogenesis of retinal detachment with morning glory disc and optic pit.

A child with nonrhegmatogenous retinal detachment associated with morning glory disc underwent first a vitrectomy and then, some months later, an optic nerve sheath fenestration. The latter procedure led to retinal reattachment. It also produced a biopsy specimen that confirmed the perineural hemiation of poorly differentiated retinal tissue in this condition, similar to that in congenital pit of the optic nerve. It demonstrated continuity of the vitreous cavity with the perineural space, both histologically and by the fact that gas injected through the pars plana into the vitreous cavity bubbled out the window in the optic nerve sheath. The authors suggest that morning glory disc and optic pit share similar anatomic features, differing more in degree than in kind, and that the porous nature of the poorly differentiated tissue herniated around the optic nerve into thesubarachnoid space in these conditions makes several sources of subretinal fluid possible.

Histopathology of Uveal Melanomas Treated with Charged Particle Radiation

The authors have treated 255 uveal melanomas with helium ion radiation. Twenty-three eyes have been enucleated because of complications and five eyes have been obtained at autopsy. We have evaluated 27 of these eyes. Neovascular glaucoma (10 eyes), painful keratitis (6 eyes), continued tumor growth (4 eyes), and vitreous hemorrhage (2 eyes) were the major complications of treatment that led to enucleation. The degree of tumor necrosis correlated with the size, pigmentation, and anterior extent of the tumor. It did not correlate with the interval from irradiation or with the amount of tumor shrinkage. Mitotic figures were extremely rare in treated tumors, suggesting that the tumor cells have lost their ability to cycle.

A Histopathologic Study of the Position of the Shearing Intraocular Lens in the Posterior Chamber

Three human eyes that had successfully undergone Shearing posterior-chamber intraocular lens implants were examined post mortem. Supporting loops of these lenses were located deep within the ciliary body adjacent to a major ciliary artery (the superior loop in two cases), within the ciliary sulcus (the superior loop in one case), within the lens capsule bag (the inferior loop in two cases), and embedded within the iris stroma (the inferior loop in one case).

Uveal tumour resection.

AIM To review the ocular retention rates, visual results, and metastases in uveal tumours managed with eye wall resection techniques. METHODS This was a retrospective analysis of consecutive local uveal tumour resections performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data were performed. RESULTS 138 eyes were scheduled for eye wall resection surgery. The mean age was 52 years (range 11–86 years). Tumours involved predominantly the iris in 14 cases, iris-ciliary body in 57, ciliary body alone in 18 patients, and in 49 cases the choroid was involved (ciliochoroidal, iris-ciliary body-choroid, or choroid). 125 eyes harboured melanomas; posterior tumours were more likely to have epithelioid cells (p<0.05). The mean follow up was 6 years. The mean clock hours in iris and iris-ciliary body tumours was 3.5. In tumours that involved the choroid the mean largest diameter was 12.9 mm and the mean thickness 8.5 mm. 105 of 138 (76%) eyes were retained. Histological assessment of surgical margins did not correlate evidence of tumour in enucleated eyes or metastatic disease. Surgical margins of more anterior tumours were more likely to be clear on histological evaluation (p<0.05). Approximately 53% of retained eyes had a final visual acuity of ⩾20/40; visual results were significantly better in more anteriorly located tumours (p<0.05). All retained iris tumour cases had ⩾20/40 final visual acuity. In tumours that involved the choroid nine of 31 retained eyes kept that level of visual acuity. Eight patients developed metastases; all metastatic events developed in patients with tumours that involved the choroid, and seven of eight were mixed cell melanomas. CONCLUSIONS 76% of eyes were retained and 53% of these had a final visual acuity of ⩾20/40. Only 7% of uveal melanoma patients developed metastatic disease with a mean follow up of 6 years. Survival did not appear to be compromised with eye wall resection and in very thick, more posterior melanomas it appeared that ocular retention and visual results were better than with radiation alone.

High-Resolution Images of Retinal Structure in Patients with Choroideremia

PURPOSE To study retinal structure in choroideremia patients and carriers using high-resolution imaging techniques. METHODS Subjects from four families (six female carriers and five affected males) with choroideremia (CHM) were characterized with best-corrected visual acuity (BCVA), kinetic and static perimetry, full-field electroretinography, and fundus autofluorescence (FAF). High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SD-OCT). Coding regions of the CHM gene were sequenced. RESULTS Molecular analysis of the CHM gene identified a deletion of exons 9 to 15 in family A, a splice site mutation at position 79+1 of exon 1 in family B, deletion of exons 6 to 8 in family C, and a substitution at position 106 causing a premature stop in family D. BCVA ranged from 20/16 to 20/63 in carriers and from 20/25 to 5/63 in affected males. FAF showed abnormalities in all subjects. SD-OCT showed outer retinal layer loss, outer retinal tubulations at the margin of outer retinal loss, and inner retinal microcysts. Patchy cone loss was present in two symptomatic carriers. In two affected males, cone mosaics were disrupted with increased cone spacing near the fovea but more normal cone spacing near the edge of atrophy. CONCLUSIONS High-resolution retinal images in CHM carriers and affected males demonstrated RPE and photoreceptor cell degeneration. As both RPE and photoreceptor cells were affected, these cell types may degenerate simultaneously in CHM. These findings provide insight into the effect of CHM mutations on macular retinal structure, with implications for the development of treatments for CHM. (ClinicalTrials.gov number, NCT00254605.).

Failure of preenucleation radiation to decrease uveal melanoma mortality

We analyzed uveal melanoma metastases in a group of 41 patients who received 20 Gy of preenucleation radiation in a Northern California Oncology Group preliminary phase I/II study, and compared their survival rates with a retrospective control group of 31 patients with characteristics matching the entrance criteria but treated with enucleation alone. Using the Cox proportional hazards model, we found that increased tumor diameter, mixed or epithelioid cell type, and radiation adversely affected survival. In vivo studies of cell cycling indicated that 20 Gy of preenucleation radiation appeared to diminish the reproductive integrity of the tumor cells. It is most likely that the failure of preenucleation irradiation to prolong patient survival was because of micrometastases that occurred before treatment.

A new mutation (Leu569Arg) within Exon 13 of the TGFBI (BIGH3) gene causes lattice corneal dystrophy type I

PURPOSE To describe an American family with lattice corneal dystrophy type I, which associates with a novel mutation, Leu569Arg, of the TGFBI (BIGH3) gene. DESIGN Experimental study. METHODS Genomic DNA was extracted from buccal epithelial cells of four affected members of an American family with lattice corneal dystrophy type I. All 17 exons of the TGFBI gene were evaluated by PCR amplification and direct sequencing. Clinical and histologic data were also collected. RESULTS Three generations of this family have been positively diagnosed with lattice corneal dystrophy, indicating autosomal dominant inheritance. We identified a heterozygous point mutation that associates with the disease phenotype. The single base-pair substitution (T1753G) results in an amino acid substitution (Leu569Arg) in exon 13 of the TGFBI gene. CONCLUSIONS Substitution of arginine for leucine at position 569 of the TGFBI gene results in a form of lattice corneal dystrophy that is phenotypically similar to other genetically distinct forms of type I disease. This is the first report of disease correlated with changes in exon 13 of the TGFBI gene.

Uveal Melanoma Necrosis After Helium Ion Therapy

A 71-year-old man underwent enucleation because of intractable pain ten months after receiving helium ion therapy for a uveal melanoma. There was no clinical or ultrasonographic evidence of tumor regression but histologically the tumor appeared almost entirely necrotic.