Lisa S. Schocket

Foveolar Choroidal Hemodynamics in Proliferative Diabetic Retinopathy

Purpose: We studied the choroidal circulation in patients with proliferative diabetic retinopathy (PDR) to assess whether choroidal hemodynamic abnormalities may exist in PDR. Methods: Eighteen eyes of 18 patients with PDR and high-risk characteristics for visual loss were included in this study. Mean duration of diabetes was 20 ± 9 years (mean ± SD), hemoglobin A1c was 8.9 ± 2.3%, and blood glucose at the time of blood flow measurement was 188 ± 90 mg/dl. Choroidal circulatory parameters obtained in these patients were compared to those of 35 eyes of 35 age and blood pressure matched, healthy controls using a Wilcoxon rank sum test. Laser Doppler flowmetry (Oculix) was used to calculate relative choroidal blood velocity (Chvel), volume (Chvol), and flow (Chflow) in the center of the foveola. Results: No significant differences in average age, mean blood pressure (BPm), or perfusion pressure (PP) were observed between diabetic patients and control subjects. In diabetic patients, Chvol was 0.29 ± 0.08 (mean ± 1 SD) arbitrary units (AU); this value was 15% lower than that of control subjects, 0.34 ± 0.10 AU (p = 0.04). In contrast, average Chvel was not significantly different between subjects with PDR (0.39 ± 0.07 AU) and control subjects (0.41 ± 0.07 AU). The average Chflow in subjects with PDR (9.4 ± 2.9 AU) was 27% lower than that of control subjects (12.8 ± 4.2 AU; p = 0.003). No significant correlation was detected between the circulatory measurements and age, BPm, or PP. There was a statistically significant negative correlation between duration of diabetes and Chvel (R = −0.55; p = 0.03). Conclusions: Our results suggest that Chvol and Chflow are significantly reduced in patients with PDR.

The effect of pregnancy on retinal hemodynamics in diabetic versus nondiabetic mothers.

PURPOSE To investigate retinal circulatory changes that occur during the third trimester of pregnancy in diabetic patients and control subjects. METHODS Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to assess the retinal circulation in seven pregnant diabetic patients and 13 age-matched pregnant control subjects. Retinal venous diameter (D), maximum erythrocyte velocity (Vmax), and retinal volumetric blood flow rate (Q) were measured in one eye of each subject during the third trimester of pregnancy (DPREG, VmaxPREG, and QPREG, respectively). These measurements were repeated during the postpartum period for both diabetic patients (11+/-7 weeks postpartum) and control subjects (16+/-6 weeks postpartum; P = .203; DPOST, VmaxPOST, and QPOST). RESULTS In control subjects, DPREG was significantly reduced by -4.5%+/-4.4% (mean percent difference +/-1 standard deviation; paired t test, P =.006) relative to DPOST. In diabetic women, DPREG was also significantly reduced by -8.1%+/-3.2% compared with DPOST (P = .001), a change that was significantly larger than that seen in control subjects (unpaired t test; P = .035). Compared with QPOS T, QPREG was reduced by -7.1%+/-14.2% (P = .123), in control subjects. In diabe tic women, QPREG was significantly decreased by -18.4%+/-9.3% compared with QPOST (P = .012). This reduction in QPREG was significantly greater in diabetic patients than in nondiabetic control subjects (unpaired t test, P = .040). No significant differences between VmaxPREG and VmaxPOST were observed in either diabetic patients (-3.1%+/-12.9%; P =.400) or control subjects (+1.9%+/-14.4%; P = .787). CONCLUSIONS Retinal venous diameter is decreased during the third trimester of pregnancy in both diabetic and nondiabetic mothers. This decrease is significantly larger in diabetic than in nondiabetic mothers. In addition, we observed a reduction in retinal volumetric blood flow in diabetic patients during pregnancy that was significantly larger than that present in nondiabetic women. This fall in retinal volumetric blood flow in diabetic patients may exacerbate retinal ischemia and hypoxia and thus may be associated with the progression of diabetic retinopathy.

Bilateral optic nerve infiltration in central nervous system leukemia

PURPOSE To report the case of a 58-year-old man with sequential bilateral retrolaminar leukemic infiltration of the optic nerves who presented with normal-appearing optic nerves and no optic nerve enhancement. DESIGN Interventional case report. METHODS A 58-year-old man with chronic myelogenous leukemia (CML) developed progressive vision loss to no light perception in both eyes over four days. The patient received 14 doses of external beam irradiation and 10 cycles of intrathecal cytarabine. Despite treatment, he developed optic nerve pallor, and visual acuity remained no light perception in both eyes. CONCLUSIONS In a patient with leukemia, leukemic optic nerve infiltration may occur even with normal-appearing optic nerves and a normal magnetic resonance image. It is important to maintain a high clinical suspicion for optic nerve infiltration so that prompt local irradiation may be initiated.

Effect of oral felodipine on ocular circulation.

AbstractPurpose: To evaluate the effects of felodipine, a calcium channelblocker, on ocular circulation. Methods: In a double blind, randomized,crossover design, 10 volunteers received placebo or felodipine on 2 separatedays. Bidirectional laser Doppler velocimetry (BLDV), laser Doppler flowmetry(LDF), and monochromatic fundus photography (MFP) were employed to assessretinal, choroidal, and optic nerve rim circulatory parameters. Measurements wereobtained at baseline, 1.5, and 3 hours after dosing. Blood pressure, intraocularpressure (IOP), and heart rate were monitored, and perfusion pressure (PP) wascalculated. Results: In comparison to placebo, significant average percentagedecreases in diastolic blood pressure (BPd; p = 0.001), mean blood pressure (BPm;p = 0.003), and perfusion pressure (PP; p = 0.003) were observed 1.5 hours following felodipine. No significant differences were observed following placebo. Retinal, choroidal and optic nerve rim circulatory parameters showed no significant changes after placebo or felodipine. A significant positive correlation between BPd and optic nerve velocity (ONvel) was observed 3 hours following felodipine (R = +0.654; p = 0.040). In contrast, no significant correlation between BPd and ONvel was noted (R = +0.198; p = 0.583) following placebo. Conclusions: No significant change in retinal, optic nerve rim, or foveolar choroidal blood flow were observed, a factor that may be important in the treatment of systemic hypertension in patients with glaucoma. Abbreviations:BLDV – Bidirectional laser Doppler velocimetry;BPd – diastolic blood pressure;BPm – mean blood pressure;BPs – systolic blood pressure;CHflow – choroidal flow;CHvel – choroidal velocity;CHvol – choroidal volume;D – vessel diameter;LDF – Laser Doppler flowmetry;MFP – monochromatic fundus photography;ONflow – optic nerve flow;ONvel – optic nerve velocity;ONvol – optic nerve volume;PP – perfusion pressure;Q – retinal volumetric blood flow rate;Vmax – maximum velocity of whole blood;Vmean – mean velocity of whole blood.

Effect of hypertension on foveolar choroidal haemodynamics

Aims: To assess the effect of systemic hypertension on the choroidal circulation in subjects with a normal eye examination. Methods: Laser Doppler flowmetry was used to determine relative choroidal blood velocity (Chvel), volume (Chvol), and flow (Chflow) in the centre of the fovea. Measurements were obtained in 15 eyes of 15 subjects with systemic hypertension. The mean average duration of hypertension was 11 (SD 6) years. Findings obtained in these patients were compared with those of 15 eyes of 15 age matched healthy controls. All subjects had normal eye examinations. Results: No significant differences in Chvel, Chvol, and Chflow, were found between the subjects with and without systemic hypertension despite a 17% higher perfusion pressure (PP) in patients with hypertension. No significant correlation was found between mean arterial pressure or PP and the choroidal circulatory parameters. It was estimated that there is a 90% power to detect a 35% difference in Chflow between the two groups. Conclusion: Systemic hypertension does not seem to have a large effect on the choroidal circulation in hypertensive patients that are controlled by antihypertensive therapy. Further studies are needed to elucidate whether systemic hypertension has an effect on the choroidal circulation in patients with ocular diseases.

Primary adrenal lymphoma with choroidal metastases.

PURPOSE To describe a 71-year-old man with bilateral primary adrenal lymphoma with metastases to the choroid. DESIGN Interventional case report. METHODS A 71-year-old man presented with decreased visual acuity in his left eye secondary to an exudative retinal detachment. Abdominal computed tomography and percutaneous biopsy revealed non-Hodgkin large-cell lymphoma involving both adrenal glands. RESULTS Ocular and adrenal lesions resolved after six cycles of chemotherapy with cytoxan, adriamycin, vincristine, and prednisone. Seven years after his initial diagnosis, the patient reported no recurrence of either ocular or systemic lymphoma. CONCLUSIONS To our knowledge, this is the first case report of bilateral primary adrenal lymphoma with apparent metastases exclusively to the eye.

Effect of laser treatment for dry age related macular degeneration on foveolar choroidal haemodynamics

Aim: Previous studies have suggested that laser photocoagulation therapy is associated with the resolution of drusen in some age related macular degeneration (AMD) patients. The main aim of the study was to determine whether low intensity laser treatment applied according to the Complications of AMD Prevention Trial (CAPT) protocol produces changes in the choroidal circulation that may help explain the mechanism leading to the resolution of drusen material. Methods: This ancillary study included 30 CAPT patients with bilateral drusen that were treated and followed at the University of Pennsylvania. Laser Doppler flowmetry was used to measure relative choroidal blood velocity (Chvel), volume (Chvol), and flow (Chflow) in the centre of the fovea. Measurements were obtained through a dilated pupil in both eyes of each patient at the initial CAPT visit before laser treatment was applied in one eye. Measurements were repeated in both eyes of each subject three months later. Analysis of laser Doppler measurements was performed in a masked fashion. Results: In comparison to baseline, no significant differences in Chvel, Chvol, or Chflow were observed three months following the application of low intensity laser according to the CAPT protocol in the untreated and treated eyes. In comparison to the untreated eyes, no significant differences were detected in the treated eyes. Based on the variability of flow measurements in the untreated eyes, the authors estimated an 85% power to detect a 15% change in relative blood flow. Conclusions: The results suggest that large alterations in choroidal blood flow do not occur at three months after low intensity laser therapy following the CAPT protocol.

PERSISTENT RETINAL CHANGES AFTER INTRAVITREAL OCRIPLASMIN.

BACKGROUND/PURPOSE Postmarket analysis helps identify potentially important side effects not discovered during clinical trials. Ocriplasmin is a recently approved medication administered by intravitreal injection for the treatment of symptomatic vitreomacular adhesion and macular hole. Overall, clinical trials of ocriplasmin have shown a relatively high safety profile. However, recently, a series of case reports have highlighted acute vision loss associated with abnormal findings on spectral domain optical coherence tomography and electroretinography. METHODS/RESULTS A 70-year-old man developed multiple discrete pockets of macular subretinal fluid 10 weeks after intravitreal ocriplasmin injection, with minimal resolution of fluid over 11 months. Electroretinographic findings demonstrated persistent rod photoreceptor sensitivity loss at 14 months after injection. CONCLUSION This is the first report of persistent electroretinographic and optical coherence tomographic abnormalities after ocriplasmin injection. Electroretinography abnormalities were noted in a small percentage of patients during ocriplasmin clinical trials and in a recent series of case reports and postmarket survey analysis. The authors propose that cleavage of fibronectin and laminin causes disruption of the interphotoreceptor matrix, leading to the ellipsoid layer attenuation and resultant electroretinographic sensitivity loss and subretinal fluid described on spectral domain optical coherence tomography. Persistent changes over 14 months in this patient indicate that ocriplasmin may have the potential to cause permanent retinal damage.

Acute Retinal Necrosis After Administration Of Adalimumab, A Systemic Antitumor Necrosis Factor Antibody

Purpose: To report a case of acute retinal necrosis in a patient on anti–tumor necrosis factor &agr; immunosuppressive therapy. Methods: Case report. Results: A 47-year-old man with psoriasis presented with blurred vision and floaters in the left eye 4 days after receiving his fourth dose of adalimumab, a tumor necrosis factor &agr; antagonist. He was diagnosed with acute retinal necrosis and was treated with intravenous acyclovir as well as prophylactic laser barricade. Seven years later, he is 20/20 with no history of a retinal detachment. Conclusion: Physicians prescribing tumor necrosis factor &agr; antagonist immunosuppressive therapy should be aware of the potential of developing acute retinal necrosis.