In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT.

Non-invasive methods of probing retinal function are of interest for the early detection of retinal disease. While retinal function is traditionally directly measured with the electroretinogram (ERG), recently functional optical imaging of the retina has been demonstrated. In this manuscript, stimulus-induced, intrinsic optical scattering changes in the human retina are measured in vivo with high-speed, ultrahigh resolution optical coherence tomography (OCT) operating at 50,000 axial scans per second and ~3.3 micron axial resolution. A stimulus and measurement protocol that enables measurement of functional OCT retinal signals is described. OCT signal changes in the photoreceptors are demonstrated. Two distinct responses having different temporal and spatial properties are reported. These results are discussed in the context of optical intrinsic signals measured previously in the retina by fundus imaging and scanning laser ophthalmoscopy. Finally, challenges associated with in vivo functional retinal imaging in human subjects are discussed.

Ultrahigh resolution optical coherence tomography in non-exudative age related macular degeneration.

AIM: To describe the appearance of the non-exudative forms of age related macular degeneration (AMD) as imaged by ultrahigh resolution optical coherence tomography (UHR-OCT). METHODS: A UHR-OCT ophthalmic imaging system, which utilises a femtosecond laser light source capable of approximately 3 mum axial resolution, was employed to obtain retinal cross sectional images of patients with non-exudative AMD. Observational studies of the resulting retinal images were performed. RESULTS: 52 eyes of 42 patients with the clinical diagnosis of non-exudative AMD were imaged using the UHR-OCT system. 47 of the 52 (90%) eyes had the clinical diagnosis of drusen and/or retinal pigment epithelial (RPE) changes. In these patients, three patterns of drusen were apparent on UHR-OCT: (1) distinct RPE excrescences, (2) a saw toothed pattern of the RPE, and (3) nodular drusen. On UHR-OCT, three eyes (6%) with a clinical diagnosis of non-exudative AMD had evidence of fluid under the retina or RPE. Two of these three patients had findings suspicious for subclinical choroidal neovascularisation on UHR-OCT. CONCLUSION: With the increased resolution of UHR-OCT compared to standard OCT, the involvement of the outer retinal layers are more clearly defined. UHR-OCT may allow for the detection of early exudative changes not visible clinically or by angiography.

Cytomegalovirus retinitis in an infant with acquired immunodeficiency syndrome.

A case of cytomegalovirus retinitis in an infant with acquired immunodeficiency syndrome (AIDS) is described. Although well recognized as an ocular manifestation of AIDS in adults, only one case of the necrotic retinitis caused by cytomegalovirus has been described in a child with AIDS. Intravenous treatment with ganciclovir resulted in substantial ocular improvement, despite the advanced nature of the disease in one eye in which there was also secondary neovascular glaucoma. Home maintenance treatment was used via Broviac catheter. The patient later died following pulmonary infection with Pneumocystis carinii.

Anterior location of the crossing artery in branch retinal vein obstruction.

We evaluated retrospectively the cases of 25 patients (26 eyes) with a recent, temporal, branch retinal vein obstruction to determine the relative anatomic position of the obstructed vein in relation to its crossing artery. In 26 (100%) of 26 eyes, the artery lay anterior to the vein, toward the vitreous cavity. A control group was obtained by evaluating the relative anatomic position between the branch retinal artery and vein at an equivalent crossing site along the opposite vascular arcade within the same eye. In the control crossing sites, the artery lay anterior to the vein 65% (15/23) of the time. We conclude that the likelihood that the artery will lie anterior to the obstructed vein at the site of blockage in a branch retinal vein obstruction is substantially greater than what would be expected by chance alone. This anatomic relationship between artery and vein probably plays a role in the cause of a branch retinal vein obstruction and may have therapeutic significance in light of a recent report concerning surgical treatment of such obstructions.

Noncontiguous local recurrence of posterior uveal melanoma after cobalt 60 episcleral plaque therapy.

Four patients with posterior uveal melanomas treated by cobalt 60 episcleral plaque therapy developed the intraocular recurrence of choroidal melanoma at a site distant from and noncontiguous to their original lesions. Three of the four patients died of metastatic melanoma. The proportion of eyes with posterior uveal melanoma treated with cobalt 60 brachytherapy who subsequently develop this type of local recurrence appears to be low (0.68%).

A prospective study of acute central retinal artery obstruction. The incidence of secondary ocular neovascularization.

We conducted a prospective study to determine the incidence of ocular neo-vascularization following acute central retinal artery obstruction. Only patients initially evaluated within 7 days of visual loss were eligible. Any patient with pre-existing ocular neovascularization or clinical evidence of the ocular ischemic syndrome noted at the initial evaluation was excluded. During the 18-month study, 33 consecutive patients were enrolled. Six patients subsequently developed neovascularization of the iris, an incidence of 18.2%. In these six patients, neovascularization of the iris appeared as early as 12 days to as late as 15 weeks following the artery obstructions. Five of the six patients (15.2% of the total) later developed neovascular glaucoma. Another patient in this series developed neovascularization of the optic disc without neovascularization of the iris, an incidence of 3.0%. Only two of the seven patients with ocular neovascularization had ipsilateral hemodynamically significant carotid artery disease as determined by noninvasive carotid artery testing. This study confirms results of previous retrospective studies that the incidence of ocular neovascularization after central retinal artery obstruction is higher than commonly thought. It also shows that, in the majority of cases, carotid artery disease is not responsible for the neovascularization seen after central retinal artery obstruction.

Endophthalmitis after pediatric strabismus surgery.

OBJECTIVE: To report 6 cases of endophthalmitis after pediatric strabismus surgery. METHODS: Retrospective review of initial signs, clinical findings, treatment, culture results, and visual and anatomical outcomes in 6 eyes of 6 children treated at 2 tertiary care institutions between 1983 and 1998. RESULTS: Four boys and 2 girls aged 8 months to 6 years (median age, 2 years) developed lethargy and asymmetric eye redness, with or without eyelid swelling or fever, within 4 days of surgery. At diagnosis (median, postoperative day 6) clinical findings included periorbital swelling, redness and leukocoria due to vitritis, and, in some cases, hypopyon. Treatment included pars plana vitrectomy and intravitreal and systemic antibiotics in all cases. Vitreous cultures grew Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Within 6 months of strabismus surgery, visual acuity was no light perception in all eyes and 3 eyes had been enucleated. The 3 remaining eyes were prephthisical. CONCLUSIONS: Endophthalmitis after pediatric strabismus surgery is rare. Children may not recognize or verbalize symptoms. Causative organisms are virulent. Visual and anatomical outcomes are poor. Lethargy, asymmetric eye redness, eyelid swelling, or fever in the postoperative period, even if initial postoperative examination results are normal, should prompt urgent ocular examination. The diagnosis of endophthalmitis may be made when biomicroscopic or indirect ophthalmoscopic examination confirms the presence of vitreous opacification with or without hypopyon. Arch Ophthalmol. 2000;118:939-944

Melanogenic neuroectodermal tumor of the retina (primary malignant melanoma of the retina).

A 35-month-old girl with leukocoria was clinically diagnosed with unilateral sporadic retinoblastoma. Macroscopic examination of her enucleated eye disclosed a white retinal tumor that appeared to be a retinoblastoma. Histopathologic examination, however, revealed that the tumor was composed of poorly differentiated neuroblastic cells, larger spindle-shaped cells, and anaplastic epithelioid cells, which is inconsistent with retinoblastoma. Immunohistochemical testing disclosed that the tumor cells were immunoreactive for melanoma-specific antigen HMB-45, while electron microscopy showed premelanosomes in the tumor cells, both of which are consistent with melanogenesis. To our knowledge, such an ocular tumor has not been reported previously.

Acquired immunodeficiency syndrome--associated herpes simplex virus retinitis. Clinical description and use of a polymerase chain reaction--based assay as a diagnostic tool.

OBJECTIVES: To describe 2 patients with acquired immunodeficiency syndrome who experienced a rapidly progressive, bilateral retinitis due to herpes simplex virus (HSV) (1 case due to HSV type 1 [HSV-1] and 1 case due to HSV type 2 [HSV-2] and to present a novel diagnostic polymerase chain reaction (PCR)-based assay. METHODS: The presentation, clinical course, and diagnostic PCR-based assay used to make the diagnosis of HSV retinitis in 2 patients with acquired immunodeficiency syndrome are described. RESULTS: Both patients experienced a rapidly progressive, bilateral retinal necrosis associated with intraretinal hemorrhages and a diffuse vasculitis. The PCR-based assays demonstrated HSV DNA in the vitreous specimens from the 2 patients. Restriction analysis on the amplified DNA showed HSV-1 in 1 patient and HSV-2 in the second patient. The diagnosis was supported in both patients by the occurrence of a herpes simplex-like encephalitis, and in 1 patient by a positive vitreous culture. The HSV-1-associated vasculitis affected primarily the retinal arterioles, with marked capillary dropout and occlusion of larger arcade vessels. In contrast, the HSV-2-associated vasculitis affected the retinal veins more than the arterioles, and was associated with an exudative retinal detachment. CONCLUSIONS: To our knowledge, these are the first 2 patients with acquired immunodeficiency syndrome in whom HSV has been implicated as the sole cause of a rapidly progressing, necrotizing retinitis. Combined PCR and restriction analysis of vitreous samples from such patients is a useful and highly specific means of diagnosing HSV-1 and HSV-2 retinitis.

Quantitative assessment of macular edema with optical coherence tomography.

OBJECTIVE: To evaluate optical coherence tomography, a new technique for high-resolution cross-sectional imaging of the retina, for quantitative assessment of retinal thickness in patients with macular edema. DESIGN: Survey examination with optical coherence tomography of patients with macular edema. SETTING: Referral eye center. PATIENTS: Forty-nine patients with the clinical diagnosis of diabetes or diabetic retinopathy and 25 patients with macular edema secondary to retinal vein occlusion, uveitis, epiretinal membrane formation, or cataract extraction. MAIN OUTCOME MEASURES: Correlation of optical coherence tomograms with slit-lamp biomicroscopy, fluorescein angiography, and visual acuity. RESULTS: Optical coherence tomograms of cystoid macular edema closely corresponded to known histopathologic characteristics. Quantitative measurement of retinal thickness is possible because of the well-defined boundaries in optical reflectivity at the inner and outer margins of the neurosensory retina. Serial optical coherence tomographic examinations allowed tracking of both the longitudinal progression of macular thickening and the resolution of macular edema after laser photocoagulation. In patients with diabetic retinopathy, measurements of central macular thickness with optical coherence tomography correlated with visual acuity, and optical coherence tomography was more sensitive than slit-lamp biomicroscopy to small changes in retinal thickness. CONCLUSIONS: Optical coherence tomography appears useful for objectively monitoring retinal thickness with high resolution in patients with macular edema. It may eventually prove to be a sensitive diagnostic test for the early detection of macular thickening in patients with diabetic retinopathy.

Diagnosis and management of the acute retinal necrosis (ARN) syndrome.

The acute retinal necrosis (ARN) syndrome represents a specific pattern of clinical presentation for certain herpes virus infections in the posterior segment of the eye. The classically described triad of the ARN syndrome consists of (1) an arteritis and phlebitis of the retinal and choroidal vasculature, (2) a confluent, necrotizing retinitis that preferentially affects the peripheral retina, and (3) a moderate to severe vitritis. Anterior segment inflammation, optic neuritis, and late retinal detachment are also common features of this disorder. Definitive evidence now implicates at least two members of the herpes virus family; varicella zoster virus and herpes simplex virus as causative agents. This paper summarizes the clinical presentation, as well as the currently recommended treatment regimen for the ARN syndrome, highlighting recent advances that have resulted in a significant improvement in the visual prognosis for affected patients.

Infantile endogenous Candida endophthalmitis presenting as a cataract.

The most common pathogen to cause endogenous endophthalmitis is the fungus Candida albicans. Most cases involve adults who are either immunosuppressed or have a history of repeated or prolonged extracorporeal access to their circulatory system. Endogenous Candida endophthalmitis can occur in infants as well, particularly when prematurity, broad spectrum antibiotic therapy, or prior surgery are present as predisposing factors. We report the clinical and histopathological findings of an infant who developed a unilateral, sectoral lens opacity four months after undergoing treatment for disseminated candidiasis. The diagnosis of localized intralenticular fungal abscess with associated endophthalmitis was made via histopathologic examination of the aspirated lens material. Treatment with systemic antifungal agents successfully preserved the eye. In addition, we review and summarize the previously reported cases of Candida endophthalmitis in patients under one year of age.

Retinal vasculitis in Crohn's disease.

Although systemic vasculitis is a prominent part of the extraintestinal complications of Crohn's disease, the association of a retinal vasculitis with this chronic granulomatous disease of the gastrointestinal system is rare. We examined a 26-year-old woman with biopsy-proven Crohn's disease who developed a severe bilateral, obliterative retinal arteritis and phlebitis, leading to a marked loss of vision. Treatment with systemic corticosteroids and cyclophosphamide succeeded in halting progression of the disease.

Prevalence and association of asteroid hyalosis with systemic diseases.

We performed a cross-sectional study of 12,205 patients, which identified 101 patients (0.83%) with asteroid hyalosis. These patients were examined for associated systemic and ocular conditions. Diabetes mellitus was found in 29 of the patients with asteroid hyalosis (29%), as compared to ten of 101 (10%) control subjects (P = .0007). An increased prevalence of systemic arterial hypertension (61 of 101 [60%] patients with asteroid hyalosis compared with 29 of 101 [29%] control subjects; P = .0001) and atherosclerotic vascular disease (30 of 101 [30%] patients with asteroid hyalosis compared with 13 of 101 [13%] control subjects; P = .006) was also discovered in the asteroid hyalosis group. Additionally, patients with asteroid hyalosis were found to be more hyperopic than control subjects (P = .009).

Lipid exudation in age-related macular degeneration.

We reviewed the relationship between lipid exudation and subretinal neovascular membranes associated with age-related macular degeneration. The records of 500 consecutive patients with subretinal neovascular membranes caused by age-related macular degeneration were examined. Seventy-five patients (15%) (85 eyes) manifested lipid exudation in conjunction with subretinal neovascularization. Twelve patients (2.4%) (13 eyes) had a massive lipid exudative response with extensive serous retinal detachment (resembling Coats' disease). Of the 85 eyes with subretinal neovascular membranes and lipid exudation, 71 (84%) had a subretinal neovascular membrane that was classified as ill defined. Improvement of vision with or without treatment was seen in only 14 of these 85 eyes (16.4%). After comparing these 85 eyes to 94 eyes from 76 patients with age-related macular degeneration and subretinal neovascular membranes but no lipid exudation, we found that a subretinal neovascular membrane associated with lipid exudation was more likely to be ill defined (71 eyes [84%] vs 35 eyes [37%]; P = .0001), was more frequently associated with retinal pigment epithelial detachment (30 eyes [35%] vs 15 eyes [16%]; P = .0029), and was more likely not to have stabilization of visual acuity (14 eyes [16%] vs 31 eyes [33%]; P = .025).

Central retinal artery occlusion in a child with T-cell lymphoma.

PURPOSE/METHODS: Central retinal artery occlusion occurs infrequently in children. We treated a child with central retinal artery occlusion before a systemic disease was discovered. RESULTS/CONCLUSION: Vision improved after paracentesis and anticoagulation. Systemic T-cell lymphoma was subsequently diagnosed. In contrast to older patients in whom atheromatous disease is a common etiologic factor, children frequently have more obscure systemic or ocular associations. Lymphoma should be considered as a possible systemic association in cases of central retinal artery occlusion, especially in younger patients who are less at risk for the more common causes.

Ocular findings in a new heritable syndrome of brain, eye, and urogenital abnormalities.

We studied the clinical and histopathologic ocular findings in four related males with a newly recognized syndrome consisting of microphthalmos, microencephaly, mental retardation, agenesis of the corpus callosum, hypospadius, and cryptorchidism with X-linked recessive inheritance. The ocular abnormalities include microphthalmos, corneal pannus and hypoplasia, cataracts, uveal hypoplasia, retinal dysplasia, optic nerve hypoplasia, and congenital blepharoptosis. In case 4, a female twin who died in utero (at 15 weeks' gestation) showed none of the ocular abnormalities.

Combined central retinal vein occlusion and cilioretinal artery occlusion associated with prolonged retinal arterial filling.

We examined four healthy men who developed cilioretinal artery occlusion associated with central retinal vein occlusion. Unlike previously reported patients with this clinical entity, there appeared to be abnormal central retinal artery inflow, as evidenced by prolonged, irregular filling of the branch retinal arteries with intravenous fluorescein angiography. The patients were treated with systemic corticosteroids. All of the patients had initial improvement in vision. However, three of the four patients had recurrent episodes of visual loss. The final visual acuity was 20/40 or better in three of the four patients.

Optical coherence tomography of central serous chorioretinopathy.

PURPOSE: To assess the potential of a new imaging technique, optical coherence tomography, for the diagnosis and monitoring of central serous chorioretinopathy. Optical coherence tomography is a novel noninvasive, noncontact imaging modality that produces high longitudinal resolution, cross-sectional tomographs of ocular tissue. METHODS: Optical coherence tomography is analogous to ultrasound, except that it uses light rather than sound to obtain higher image resolution in the retina. Cross-sectional tomographs of optical reflectivity within the retina are produced with longitudinal resolution of 10 microns. Optical coherence tomography was used to examine 16 patients at a referral eye center whose initial examination disclosed the clinical diagnosis of central serous chorioretinopathy. The optical coherence tomography results were correlated with slit-lamp biomicroscopy, fundus photography, and fluorescein angiography. RESULTS: The cross-sectional view produced by optical coherence tomography was effective in objectively quantifying the amount of serous retinal detachment in the disease. Optical coherence tomography disclosed detachments that were undetected by slit-lamp biomicroscopy. Longitudinal measurements with optical coherence tomography were successfully able to track the resolution of subretinal fluid accumulation. CONCLUSION: Optical coherence tomography is potentially useful as a new, noninvasive diagnostic technique for quantitative examination of patients with central serous chorioretinopathy and objectively monitoring the clinical course of the serous retinal detachment in this disease.

Repair of retinitis-related retinal detachments with silicone oil in patients with acquired immunodeficiency syndrome.

To provide prompt visual rehabilitation and to reduce the need for repeated operations, we performed vitrectomy with silicone oil tamponade in 16 consecutive eyes with retinal detachments related to cytomegalovirus retinitis and acute retinal necrosis in 13 patients with acquired immunodeficiency syndrome. In all 16 eyes (100%), retinas were reattached with one operation. Preservation of ambulatory vision was achieved in six of eight eyes (75%; mean follow-up, 14.6 weeks). No patient with hand motion visual acuity or worse preoperatively recovered ambulatory vision. Visual acuity recovery was limited by optic nerve disease in five eyes (31%). Silicone oil-related side effects did not adversely affect visual outcome in any eye. Six patients (46%) have since died (mean, 4.4 months postoperatively). These data indicated that successful surgical repair of these detachments can be consistently achieved with this approach. The prognosis for ambulatory vision is strongly related to preoperative visual acuity.