Jeremiah Brown

Visual Prognosis of Multifocal Choroiditis, Punctate Inner Choroidopathy, and the Diffuse Subretinal Fibrosis Syndrome

PURPOSE To characterize the visual prognosis of patients with multifocal choroiditis and panuveitis (MCP), punctate inner choroidopathy (PIC), and the diffuse subretinal fibrosis (DSF) syndrome. METHODS Forty-one patients with MCP, 16 with PIC, and 5 with DSF syndrome were evaluated. The mean follow-up was approximately 39 months for patients with MCP, 51 months for patients with PIC, and 59 months for patients with DSF syndrome. Complete ophthalmic examinations were performed, and photofiles were reviewed. RESULTS The final average visual acuity for patients with MCP was 20/50. Forty-five of the 68 involved eyes (66%) had 20/40 visual acuity or better. Choroidal neovascularization (CNV) developed within choroiditis lesions in 22 (19 patients) of 68 eyes, causing visual acuity poorer than 20/50 in 14 eyes. The final average visual acuity in patients with PIC was 20/39; 23 (77%) of the 30 involved eyes had visual acuity of 20/40 or better. Six of the seven eyes with 20/50 or poorer vision had CNV. Six other eyes had CNV within the macula that regressed spontaneously with good resultant vision. Seven of the ten involved eyes with DSF syndrome had 20/200 or poorer vision. Poor vision was due to fibrosis and atrophy within the macula. CONCLUSION Most patients with MCP and PIC retained visual acuity of 20/40 or better. In nearly one third of patients with MCP and PIC, CNV developed. Severe visual loss in these diseases was usually due to subfoveal CNV. Patients with DSF syndrome had a poor prognosis due to fibrosis and atrophy involving the macula.

Visual acuity impairment in patients with retinitis pigmentosa at age 45 years or older

OBJECTIVE To determine the severity of visual acuity impairment in patients, age 45 years or older, with either isolated or identifiable genetic subtypes of retinitis pigmentosa (RP) and Usher syndrome. DESIGN Multicenter, retrospective, cross-sectional analysis. PARTICIPANTS Visual acuity data were obtained on 999 patients with different genetic subtypes of RP and Usher syndrome, age 45 years or older, from 4 major eye care centers in the United States. INTERVENTION The best-corrected visual acuity obtained on these patients from the eye with better vision on their most recent visit was used for the analysis. MAIN OUTCOME MEASURE Best-corrected visual acuity was the main parameter analyzed for the study, and it was obtained with Snellen or Feinbloom low vision charts or with a B-VAT II monitor (Mentor). RESULTS The final analyses were done on 982 patients (17 patients with a sector form of RP were analyzed separately). Of the 982 patients, 506 (52%) had a visual acuity of 20/40 or better, and 678 (69%) had a visual acuity of 20/70 or better in at least one eye. There were 243 (25%) patients who had a visual acuity of 20/200 or worse in both eyes. Five (0.5%) patients had no light perception in both eyes. The odds ratio for any patient having a visual acuity of 20/200 or worse in this population was 1.4 for each difference of 10 years of age. Similarly, the odds ratio of a patient having a visual acuity of 20/40 or better in at least one eye was 0.95 for a 10-year age difference. CONCLUSIONS In this large population of patients with RP and Usher syndrome from four centers, it was rare for such patients to lose all vision in both eyes. One fourth of the patients had a visual acuity of 20/200 or worse in both eyes, and more than half of the population had a visual acuity of 20/40 or better in at least one eye. These data can be used to counsel such patients on the extent of potential visual acuity impairment from their disease.

Enlarged Blind Spots in Chonoretinal Inflammatory Disorders

PURPOSE This study was undertaken to better characterize patients with multifocal choroiditis and panuveitis (MCP), punctate inner choroidopathy (PIC), multiple evanescent white dot syndrome (MEWDS), and diffuse subretinal fibrosis syndrome. The specific aim was to determine whether these disorders were different entities or part of a spectrum of diseases with similar features. METHODS Seventy-nine patients were included in this study. Most of the patients have been followed up prospectively since July 1980 with some found retrospectively. RESULTS Forty-one patients had MCP, 16 had PIC, 6 had diffuse subretinal fibrosis syndrome, and 16 had MEWDS. Patients with MCP had visual loss and visual field defects caused directly by visible lesions or recurrent inflammation around old lesions. In particular, clustering of lesions around the optic nerve and nasal periphery was seen in patients with MCP and appeared to be related to visual field loss. Patients with PIC also had enlarged blind spot and other field defects explained by fundus lesions. Patients with PIC and MCP did not have recurrent lesions on extended follow-up. Patients with diffuse subretinal fibrosis syndrome represented a subset of patients characterized with lesions in the posterior pole, sever scarring, and visual loss. Patients with MEWDS had the least inflammation with symmetrically distributed lesions. Minimal permanent chorioretinal scarring was seen in patients with MEWDS. Visual field defects improved in most patients with MEWDS and PIC, whereas most patients with MCP and diffuse subretinal fibrosis syndrome did not improve. CONCLUSIONS Although enlarged blind spots are a feature of all four disorders, other clinical, angiographic, and electroretinographic evidence suggest that these are different entities.

Transplantation of quantum dot-labelled bone marrow-derived stem cells into the vitreous of mice with laser-induced retinal injury: survival, integration and differentiation.

Accidental laser exposure to the eyes may result in serious visual impairment due to retina degeneration. Currently limited treatment is available for laser eye injury. In the current study, we investigated the therapeutic potential of bone marrow-derived stem cells (BMSCs) for laser-induced retinal trauma. Lineage negative bone marrow cells (Lin(-) BMCs) were labelled with quantum dots (Qdots) to track the cells in vivo. Lin(-) BMCs survived well after intravitreal injection. In vivo bromodeoxyuridine (BrdU) labelling showed these cells continued to proliferate and integrate into injured retinas. Furthermore, they expressed markers that distinguished retinal pigment epithelium (RPE), endothelium, pericytes and photoreceptors. Our results suggest that BMSCs participate in the repair of retinal lesions by differentiating into retinal cells. Intravitreal transplantation of BMSCs is a potential treatment for laser-induced retinal trauma.

Frequency of Optic Disc or Parapapillary Nerve Fiber Layer Drusen in Retinitis Pigmentosa

PURPOSE To determine the frequency and characteristics of optic disc and parapapillary nerve fiber layer drusen in patients with retinitis pigmentosa and to attempt to document any differences in the frequency within different genetic subtypes of retinitis pigmentosa. METHODS This retrospective case series reviewed 117 patients with autosomal-dominant, 84 with autosomal-recessive, and 61 with X-linked recessive forms of retinitis pigmentosa. Color fundus photographs were reviewed independently by three investigators. The presence of optic disc or parapapillary nerve fiber layer drusen was documented only when all three observers concurred as to their presence. The number (isolated or multiple), site (disc, parapapillary, or both), and bilaterality (unilateral or bilateral) were noted in each patient. RESULTS Optic disc or parapapillary nerve fiber layer drusen or both were observed in 11 patients (9.4%) with autosomal-dominant, 6 patients (7.1%) with autosomal-recessive, and 7 patients (11.5%) with X-linked recessive types of retinitis pigmentosa. The differences in the observed frequencies were not statistically significant (P = 0.67). Overall, the frequency of optic nerve head or parapapillary drusen or both in 262 patients with retinitis pigmentosa was 9.2%. CONCLUSION In a large population of patients with retinitis pigmentosa, our findings suggest that approximately 10% are likely to show optic nerve fiber layer drusen involving the optic disc or parapapillary regions or both. The frequency does not vary significantly between different genetic subtypes.

Comparison of the clinical expression of retinitis pigmentosa associated with rhodopsin mutations at codon 347 and codon 23.

PURPOSE To examine the difference in expression of retinitis pigmentosa from mutations at codon 23 and codon 347 or rhodopsin; to report a novel mutation in rhodopsin. METHODS Goldmann perimetry (solid angle of I4e isopter) and electroretinographic amplitudes (square root transform of a response ratio) were analyzed for 24 patients with mutations at codon 347 (15 with Pro347Ala, 2 with Pro347Gln, 6 with Pro347Leu, and 1 with a novel Pro347Cys change) and 41 patients with mutations at codon 23 (6 with Pro23Ala; 35 with Pro23His). RESULTS When all patients with mutations at codons 347 and 23 were compared, loss of visual fields was significantly worse in patients with codon 347 changes (P =.0003). Only rod responses of the electroretinograms were significantly different between the two groups (P =.048). Specific comparison of Pro347Ala with Pro23Ala using regression analysis demonstrated significant differences in severity between codon 23 and codon 347 patients for b-wave amplitudes of rod (P =.0069), cone (P =.039) and maximum combined response (P =.049). The solid angle of the I4e isopter was also significantly different (P =.025) between the groups after controlling for age. Modeling age by group for Pro347Ala comparison produced an R(2) of.44. CONCLUSION We reconfirmed that rhodopsin-related retinitis pigmentosa from mutations involving codon 347 produces a more severe phenotype than that involving codon 23. Accurate modeling of disease was shown to be possible by incorporating the effects of a patients age and specific genotype. Therefore, both of these variables must be considered in prognostic counseling and subject recruitment for future therapeutic trials.

Clinical and electroretinographic findings of female carriers and affected males in a progressive X-linked cone-rod dystrophy (COD-1) pedigree.

OBJECTIVE To study the clinical and electroretinographic findings of affected males and female carriers in a family with X-linked cone-rod dystrophy (COD-1). DESIGN Observational case series. PARTICIPANTS Twenty-five members of a five-generation pedigree were examined. METHODS A history of visual impairment including age at onset, loss of acuity, color vision abnormalities, photophobia, and nyctalopia was obtained. A complete ophthalmologic examination was performed, including kinetic perimetry with a Goldmann perimeter, FM 100-hue testing, and standardized Ganzfeld electroretinography following the ISCEV protocol. MAIN OUTCOME MEASURES Patients were classified as affected or unaffected on the basis of the clinical examination. All carrier females had affected sons. RESULTS Nine affected males and seven female carriers were identified. Affected males noted decreased visual acuity and poor color vision within the first two decades of life. Early in the disease, macular retinal pigment epithelial (RPE) changes were found that progressed to an atrophic macular scar by the fifth decade. Evidence of progression from macular pigment mottling to an atrophic macular lesion over a 13-year period was identified in one patient. The photopic, single-flash, b-wave amplitude was low in all affected males and declined with age. The 30-Hz flicker b-wave implicit times were abnormally prolonged in all affected males. Female carriers were asymptomatic although three had slightly abnormal color vision and small paracentral field defects and subtle RPE defects were found in three carriers. Carriers demonstrated prolongation of the 30-Hz flicker b-wave implicit time and interocular asymmetry. Five of seven carriers and two affected males demonstrated reduced oscillatory potentials and an abnormal-appearing flattened photopic a-wave. Five men and two women demonstrated a characteristic tapetal-like retinal sheen. CONCLUSIONS Affected patients in this pedigree demonstrate early loss of visual acuity and poor cone function with late rod involvement. Female carriers may appear clinically normal or may be identified by subtle color vision defects, fundus abnormalities, prolongation of the 30-Hz flicker implicit time with interocular asymmetry, or an abnormal flattened photopic a-wave. Genetic linkage analysis of this family was recently reported and the disease-causing gene has been mapped to an approximately 1-Mb interval on chromosome Xp11.4.

Linkage analysis of X-linked cone-rod dystrophy : Localization to Xp11.4 and definition of a locus distinct from RP2 and RP3

Progressive X-linked cone-rod dystrophy (COD1) is a retinal disease affecting primarily the cone photoreceptors. The COD1 locus originally was localized, by the study of three independent families, to a region between Xp11.3 and Xp21.1, encompassing the retinitis pigmentosa (RP) 3 locus. We have refined the COD1 locus to a limited region of Xp11.4, using two families reported elsewhere and a new extended family. Genotype analysis was performed by use of eight microsatellite markers (tel-M6CA, DXS1068, DXS1058, DXS993, DXS228, DXS1201, DXS1003, and DXS1055-cent), spanning a distance of 20 cM. Nine-point linkage analysis, by use of the VITESSE program for X-linked disorders, established a maximum LOD score (17.5) between markers DXS1058 and DXS993, spanning 4.0 cM. Two additional markers, DXS977 and DXS556, which map between DXS1058 and DXS993, were used to further narrow the critical region. The RP3 gene, RPGR, was excluded on the basis of two obligate recombinants, observed in two independent families. In a third family, linkage analysis did not exclude the RPGR locus. The entire coding region of the RPGR gene from two affected males from family 2 was sequenced and was found to be normal. Haplotype analysis of two family branches, containing three obligate recombinants, two affected and one unaffected, defined the COD1 locus as distal to DXS993 and proximal to DXS556, a distance of approximately 1.0 Mb. This study excludes COD1 as an allelic variant of RP3 and establishes a novel locus that is sufficiently defined for positional cloning.

Horner's Syndrome in Subadventitial Carotid Artery Dissection and the Role of Magnetic Resonance Angiography

PURPOSE/METHODS A 47-year-old man with a postganglionic Horners syndrome and severe right facial pain was found to have a normal carotid angiogram. We obtained a magnetic resonance angiogram of the neck because of our continued clinical suspicion of dissection. RESULT/CONCLUSION An area of hyperintensity was identified along the lumen of the right internal carotid artery, suggesting a subadventitial dissection. Magnetic resonance angiography is a noninvasive, sensitive technique for identifying some carotid dissections.

Laser-induced macular holes demonstrate impaired choroidal perfusion.

Purpose To evaluate choroidal perfusion following creation of a laser-induced macular hole in a nonhuman primate model. Methods Six rhesus monkeys underwent macular exposures delivered by a Q-switched Nd:YAG laser. The lesions were evaluated with fluorescein angiography and indocyanine green angiography using scanning laser ophthalmoscopy. Results Each lesion produced vitreous hemorrhage and progressed to a full-thickness macular hole. Indocyanine green angiography revealed no perfusion of the choriocapillaris beneath the lesion centers. Fluorescein angiography demonstrated mild enlargement of the foveal avascular zone due to loss of perifoveal capillaries. Histopathologic evaluation showed replacement of the choriocapillaris with fibroblasts and connective tissue. Conclusions Nd:YAG laser–induced macular holes result in long-term impairment of choroidal perfusion at the base of the hole due to choroidal scarring and obliteration of the choriocapillaris. Evaluation of choroidal perfusion may be useful in assessment of laser-injured patients. Impairment in choroidal perfusion may have functional implications for surviving photoreceptors.