Prospective multicenter study of visual outcomes following three different treatments for macular edema associated with branch retinal vein occlusion: a study by the Japanese BRVO study group.

PURPOSE: To evaluate the visual outcomes of three different treatments for macular edema associated with a branch retinal vein occlusion. METHODS: A 1-year, non-randomized study was conducted at 21 ophthalmological institutes in Japan. All of the patients received one of three treatments: medication per-oral (PO), photocoagulation (PC) or pars plana vitrectomy (PPV). Retinal hemorrhage that was lower than that shown in reference photographs was considered an inclusion criteria. RESULTS: Ninety-eight patients were studied. Twenty-six (26.5%) patients were in the PO, 37 (37.8%) in the PC and 35 (35.7%) in the PPV group. The mean best-corrected visual acuity (BCVA) improved significantly after 1 year in all groups (P < 0.001). There was no significant difference among those groups in the degree of the BCVA improvement. However, the BCVA in the PPV group improved significantly at 6 months, significantly earlier than in the other two groups. The BCVA at entry in the PPV group was significantly worst among patients whose eyes had a BCVA of ≥ 0.7 at 1 year (P < 0.05). CONCLUSIONS: PPV had a slight advantage over PC and PO, although the improvement to the BCVA did not differ significantly following any of the three treatments.

Ocular wavefront aberrations in patients with macular diseases.

BACKGROUND: There have been reports that by compensating for ocular aberrations using adaptive optical systems it may be possible to improve the resolution of clinical retinal imaging systems beyond what is now possible. To develop such a system to observe eyes with retinal disease, understanding of ocular wavefront aberrations in individuals with retinal disease is required. METHODS: Eighty-two eyes of 66 patients with macular disease (epiretinal membrane, macular edema, macular hole, etc.) and 85 eyes of 51 patients without retinal disease were studied. Using a ray-tracing wavefront device, each eye was scanned at both small and large pupil apertures, and Zernike coefficients up to the sixth order were acquired. RESULTS: In phakic eyes, third-order root mean square errors in the macular disease group were statistically greater than in the control group, an average of 12% for 5-mm and 31% for 3-mm scan diameters (P < 0.021). In pseudophakic eyes, there was also an elevation of third-order root mean square, on average 57% for 5-mm and 51% for 3-mm scan diameters (P < 0.031). CONCLUSION: Higher-order wavefront aberrations in eyes with macular disease were greater than in control eyes without disease. This study suggests that such aberrations may result from irregular or multiple reflecting retinal surfaces. Modifications in wavefront sensor technology will be needed to accurately determine wavefront aberration and allow correction using adaptive optics in eyes with macular irregularities.

Macular autofluorescence in eyes with cystoid macula edema, detected with 488 nm-excitation but not with 580 nm-excitation.

BACKGROUND: Fundus autofluorescence (AF) derives from lipofuscin in the retinal pigment epithelium (RPE). Because lipofuscin is a by-product of phagocytosis of photoreceptors by RPE, AF imaging is expected to describe some functional aspect of the retina. In this study we report distribution of AF in patients showing macular edema. METHODS: Three eyes with diabetic macular edema (DME) and 11 with retinal vein occlusion (RVO), associated with macular edema (ME) were examined. ME was determined by standard fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT). AF was recorded using a Heidelberg confocal scanning laser ophthalmoscope (cSLO) with 488 nm laser exciter (488 nm-AF), and a conventional Topcon fundus camera with halogen lamp exciter and 580 nm band-pass filter (580 nm-AF). Color fundus picture, FA image and these two AF images were analyzed by superimposing all images. RESULTS: All subjects presented cystoid macular edema (CME) with petaloid pattern hyperfluorescence in FA. In 488 nm-AF, all eyes (100%) showed macular autofluorescence of a similar shape to that of the CME in FA. In contrast, in 580 nm-AF only one eye (7%) presented this corresponding petaloid-shaped autofluorescence. In all cases, peripheral retinal edemas did not show autofluorescence corresponding to the leakage in FA. CONCLUSIONS: In eyes with CME, analogous hyperautofluorescence to the CME was always observed in 488 nm-AF, while it was rarely observed in 580 nm-AF. Moreover, this CME hyperautofluorescence was only seen in the macular area. We hypothesize that autofluorescence from CME may be considered as a "pseudo" or "relative" autofluorescence, due to macular stretching following CME that may result in lateral displacement of macular pigments (MPs) and subsequent reduction of MPs density, as MPs block 488 nm-AF more intensely than 580 nm-AF. Although this phenomenon may not directly indicate change of RPE function, it may be used as a method to assess or track CME non-invasively.

Photoreceptor images of normal eyes and of eyes with macular dystrophy obtained in vivo with an adaptive optics fundus camera.

PURPOSE: To report on images of the human photoreceptor mosaic acquired in vivo with a newly developed, compact adaptive optics (AO) fundus camera. METHODS: The photoreceptors of two normal subjects and a patient with macular dystrophy were examined by using an AO fundus camera equipped with a liquid crystal phase modulator. In the eye with macular dystrophy, the fixation point in the AO images was identified using scanning laser ophthalmoscope (SLO) microperimetric image superimposed on a color fundus photograph. RESULTS: Photoreceptor cells were detected as bright dots approximately 4 microm in diameter in normal subjects. In the eye with macular dystrophy, the fixation point was located within the bull's eye lesion and uniform small whitish spots with irregular patchiness were observed in the AO images of this area. The distance between the small spots was 3-4 microm. In other parts of the bull's eye retinal lesion, the whitish spots were larger and of different sizes. CONCLUSIONS: The photoreceptor mosaic could be identified in photographs of eyes of normal subjects and an eye with macular dystrophy in vivo by an AO fundus camera. In the eye with macular dystrophy, a relatively uniform photoreceptor mosaic was observed around the fixation point, whereas presumed debris of photoreceptor degradation was observed in the other bull's eye retinal lesion.

Adaptive optics fundus camera to examine localized changes in the photoreceptor layer of the fovea.

PURPOSE: To examine highly localized photoreceptor disruptions in the fovea by a high-resolution adaptive optics (AO) fundus camera combined with Fourier-domain optical coherence tomography (FD OCT). DESIGN: Observational case series. PARTICIPANTS: Three eyes of 3 patients who showed dark foveal spots by slit-lamp biomicroscopy. METHODS: Three patients who reported metamorphopsia but showed no changes in the retina in conventional fundus photographs were examined. High-resolution retinal images were obtained with the AO fundus camera and by FD OCT. The images were compared with the findings obtained by standard clinical tests, including Amsler charts and fluorescein angiography (FA). MAIN OUTCOME MEASURES: Quantitative measurements of the area of photoreceptor disruption. RESULTS: Slit-lamp biomicroscopy revealed an irregularly shaped dark spot in the fovea centralis but no changes in FA in the 3 cases. The photoreceptor mosaic was absent in a highly localized area of the fovea in the images obtained by the AO fundus camera, and the photoreceptor outer segment was absent or disturbed at the corresponding area by FD OCT in all 3 cases. The horizontal and vertical sizes of the area of disturbance of the photoreceptor mosaic in the AO images in the 3 eyes were 400x200 microm, 300x120 microm, and 300x200 microm. These sizes were comparable to the photoreceptor outer segment disturbances in the OCT images which were 330x150 microm, 280x100 microm, 200x150 microm, respectively. CONCLUSIONS: Localized OS disturbances were able to be detected in eyes with a dark foveal spot by AO fundus camera 2-dimensionally and by FD OCT axially. The good correspondence of the sizes of the area of photoreceptor disturbances obtained by AO images to those by FD OCT images indicate that the AO images can be used to evaluate and follow the 2-dimensional area of focal changes of the photoreceptors in the fovea quantitatively.

Serial measurements of higher-order aberrations after blinking in patients with dry eye.

PURPOSE: To study the sequential postblink changes in ocular higher-order aberrations (HOAs) in patients with dry eye. METHODS: A wavefront sensor was used to measure HOAs sequentially for 30 seconds in 20 eyes of 20 patients with dry eye. The 20 eyes were classified into two groups, with or without superficial punctate keratopathy (SPK) in the central cornea. During the measurement, subjects were required to blink every 10 seconds. The aberration data were analyzed in the central 4-mm diameter for coma-like, spherical-like, and total HOAs up to sixth-order Zernike polynomials. Total HOAs, as well as fluctuation index (FI) and stability index (SI) of the total HOAs over time were compared between the two groups. The sequential changes in coma-like aberration, spherical-like aberration, and total HOAs were also investigated. RESULTS: The total ocular HOAs were significantly (P = 0.001) greater in dry eyes with central SPK than in dry eyes without central SPK. The sequential pattern of the total ocular HOAs had higher initial and consistently higher values in dry eyes with central SPK, whereas that of dry eyes without central SPK showed consistently lower total HOAs that were similar to the pattern of normal eyes. CONCLUSIONS: Increased HOAs in dry eye at least partially result from SPK above the optical zone. The low tear volume in dry eye may not cause sequential increases in HOAs after blinking. Sequential measurement of HOAs may be useful for evaluating the sequential changes in optical quality in patients with dry eye.

In vivo measurements of cone photoreceptor spacing in myopic eyes from images obtained by an adaptive optics fundus camera.

PURPOSE: To determine the cone spacing in normal and myopic eyes from the images obtained by an adaptive optics (AO) fundus camera. METHODS: Nineteen eyes of 19 healthy volunteers with a mean +/- SD spherical equivalent refractive error of -3.7 +/- 3.3 diopters (D) (range, -0.3 to -11.1 D) and a mean axial length of 25.4 +/- 1.61 mm (range, 23.4-28.0 mm) were investigated in a prospective cross-sectional study. An AO fundus camera equipped with a liquid crystal phase modulator was used to obtain the images of the photoreceptor mosaic. The spacing between the cones was calculated manually at a retinal locus 2 degrees temporal from the center of the fovea. The magnification of the image was calculated by the axial length measured with an IOL Master. RESULTS: The axial length was correlated with the refractive error (Pearson, r = -0.869; P < 0.001). The average cone spacing in the moderate- to high-myopia group (-6.5 +/- 2.3 D, n = 9) was 4.71 +/- 0.44 microm, which was significantly greater (P = 0.002) than the 3.90 +/- 0.47 microm in the normal and low-myopia groups (-1.1 +/- 0.9 D, n = 10). The cone spacing was significantly correlated with the axial length (r = 0.77, P < 0.001). CONCLUSIONS: The AO fundus camera is capable of acquiring images of the photoreceptors in normal and myopic eyes. The greater spacing between cones in the myopia group is consistent with histological findings. These results suggest that retinal expansion should be considered in addition to Knapp's law when aniseikonia is evaluated in axial myopia.

Magnitude and orientation of Zernike terms in patients with keratoconus.

PURPOSE: To measure the magnitude and orientation of the Zernike terms in keratoconic eyes, with and without rigid gas-permeable (RGP) contact lenses. METHODS: A total of 76 eyes with keratoconus, 58 eyes with keratoconus suspect, and 105 normal eyes were studied. To determine the effect of RGP lenses, 19 eyes with keratoconus, 9 eyes with keratoconus suspect, and 17 normal eyes, with and without an RGP lenses, were compared. Ocular higher-order aberrations (HOAs) were measured with a wavefront sensor for a 4-mm-diameter pupil, and the magnitudes, axes of trefoil, and coma were calculated by vector analysis. RESULTS: Zernike vector analysis showed prominent vertical coma with an inferior slow pattern, with mean axes of 82.5 degrees or 91.0 degrees in the patients with keratoconus or keratoconus suspect, respectively. The mean axes of trefoil in patients with keratoconus (93.8 degrees ) and keratoconus suspect (100.6 degrees ) differed from that in normal subjects (35.4 degrees ), indicating that keratoconus has a reverse trefoil pattern from that of normal eyes. Although the total HOAs were significantly (keratoconus and keratoconus suspect, P < 0.001 and P = 0.012, respectively) reduced with an RGP lens, the patterns of the axes of coma and trefoil were reversed with the lens. CONCLUSIONS: In addition to the larger amount of trefoil, coma, tetrafoil, and secondary astigmatism, keratoconic eyes tend to have a reverse coma pattern and reverse trefoil aberrations compared with normal eyes. Although RGP lenses correct the irregular astigmatism, smaller comet-like retinal images in the opposite direction remain due to residual vertical coma.

Automated keratoconus detection using height data of anterior and posterior corneal surfaces.

PURPOSE: To develop a keratoconus detection algorithm using the corneal topographic data of the anterior and posterior corneal surfaces. METHODS: Topographic measurements of the cornea were made with a slit-scanning corneal topographer. We examined 120 subjects (165 eyes); keratoconus patients and keratoconus suspect patients comprised the keratoconus group, and post-photorefractive keratectomy patients, with-the-rule astigmatism patients, and controls without disease comprised the nonkeratoconus group. Two variables of the anterior corneal surface, two variables of the posterior corneal surface, and one corneal thickness variable were obtained by applying the Fourier harmonic decomposition formula. By performing a logistic regression analysis with a training set to differentiate the keratoconus group from the nonkeratoconus group, the Fourier-incorporated keratoconus detection Index (FKI) was created. The validity of the FKI was determined by using independent validation sets. RESULTS: The FKI distinguished the keratoconus group from the nonkeratoconus group with 96.9% sensitivity and 95.4% specificity in the validation set. CONCLUSIONS: A newly developed automated keratoconus classifier can be used to screen keratoconic patients. The index is based on information obtained by Fourier analysis from not only the anterior corneal surface but also from the posterior corneal surface and corneal thickness.

Serial measurements of higher-order aberrations after blinking in normal subjects.

PURPOSE: To investigate sequential changes in the optical quality of normal eyes associated with blinking. METHODS: Ocular higher-order aberrations (HOAs) were measured sequentially by using a wavefront sensor for 30 seconds in 20 eyes of 20 normal subjects. During the measurement, subjects were forced to blink every 10 seconds. The obtained aberration data were analyzed in the central 4-mm diameter for coma-like, spherical-like, and total HOAs up to the sixth-order Zernike polynomials. RESULTS: The serial changes in the HOAs with blinking were classified into four groups by pattern: stable (25%), small-fluctuation (45%), sawtooth (20%), and others (10%). In the subjects with the sawtooth pattern, the total HOAs increased significantly (P < 0.001, one-way repeated-measures ANOVA) with time between blinks. Increased total HOAs and coma-like aberrations in the subjects with the sawtooth pattern suggested that the inferosuperior asymmetric change in tear film thickness is responsible. CONCLUSIONS: Dynamic changes in HOAs after blinking showed variations even in clinically normal subjects. Serial measurements of HOAs may be useful in evaluating the dynamic changes in tear film and the effects on the quality of vision after blinking.

Intensity analysis of Hartmann-Shack images in cataractous, keratoconic, and normal eyes to investigate light scattering.

PURPOSE: A clinical investigation of novel methods for evaluating light scattering using a Hartmann-Shack aberrometer. METHODS: Aberrometry was performed on normal eyes (n=7; patient age, 26.7+/-2.5 years, mean+/-SD), eyes with keratoconus (n=22; patient age, 26.1+/-8.1 years), and eyes with cataract (n=17; patient age, 56.5+/-16.9 years) using a Hartmann-Shack wavefront aberrometer. We introduced two methods: (1) a contrast method, in which we calculated the inverse of contrast of the local images around 12 spots in a Hartmann-Shack image, and (2) a difference of point spread function (PSF) method, in which we analyzed the difference between the width of the PSF computed with aberration information and the width of the measured PSF, which contains both aberration and light scattering information. RESULTS: The inverse contrast in cataractous eyes (5.04+/-3.06 inverse contrast units) was significantly larger than that in normal eyes (1.57+/-0.56) or keratoconic eyes (1.83+/-0.79). The difference of PSF in cataractous eyes (81.8+/-65.2 microm) was also significantly larger than that in normal eyes (9.3+/-4.3 microm) or keratoconic eyes (30.0+/-20.1 microm). The inverse contrast and the difference in the PSF were highly correlated (r=0.89, P<0.0001). CONCLUSIONS: The two methods introduced here successfully distinguished cataractous eyes from normal and keratoconic eyes. After the results were analyzed by a discriminant analysis, the separation of the three categories proved to be excellent.

Intravitreal toxicity of the kenalog vehicle (benzyl alcohol) in rabbits.

PURPOSE: To test the toxicity of intravitreal injections of benzyl alcohol. METHODS: Nine New Zealand rabbits were injected with either a control or a test article at elevating concentrations. The test article was benzyl alcohol calculated to give final injected concentrations of 0.0073%, 0.022%, 0.073%, 0.222%, and 0.733% benzyl alcohol. The 0.022% concentration corresponds to the concentration of benzyl alcohol in human eyes when 0.1 mL of commercial Kenalog (Bristol-Myers Squibb, Princeton, NJ) is used. Baseline examination of the rabbits was performed along with postinjection examinations on days 1, 3, 7, and 14. The eyes were enucleated and examined by light and electron microscopic examinations. RESULTS: Eyes injected with benzyl alcohol concentrations of 0.073%, 0.222%, and 0.733% displayed changes in the outer retina including loss of, and shortening of, outer segments and photoreceptors. CONCLUSIONS: Benzyl alcohol at concentrations modestly higher than what is present in commercial Kenalog is toxic to the rabbit eye. This has been shown in other organ systems. If commercial preserved Kenalog is to be used clinically, decanting the supernatant or using other means to remove the benzyl alcohol may be considered, especially if a volume of >0.1 mL of solution is used. We hypothesize that the noninfectious inflammation seen clinically after Kenalog injection is due to the presence of a toxic preservative at unsafe concentrations.

Wavefront analysis of eyes with cataracts in patients with monocular triplopia.

PURPOSE: To determine whether wavefront analysis using a Hartmann-Shack (H-S) aberrometer can reveal the cause of monocular triplopia in eyes with mild cataracts. METHODS: Six patients (nine eyes; age range 38-58 years; average 49.8 +/- 6.9 years) who complained of monocular triplopia at the Osaka University Hospital between January and December 2003 were examined. Wavefront analyses of ocular and corneal aberrations of the central 4 mm diameter were performed using a H-S aberrometer equipped with a Placido ring videokeratoscope. The ocular and corneal higher-order wavefronts were fitted with a fourth-order Zernike expansion. RESULTS: All nine eyes showed mild nuclear cataract and had a mean spherical refractive error of -10.3 +/- 3.5 D. The visual acuity was > or = 20/40 except in one eye with glaucoma. For the Zernike polynomials, the trefoil aberration (C3-3) and the spherical aberration (C40) were significantly higher than those of age-matched normal controls (p < 0.001). The simulated retinal image of a Landolt C showed that the combination of trefoil aberration and the spherical aberration can cause an image with a triple configuration. CONCLUSIONS: Monocular triplopia was reported by middle-aged patients with mild nuclear cataract and high myopia. Wavefront analyses suggested that the triple configuration was caused by the combined increase of the trefoil and spherical aberration in lenses with mild nuclear cataracts.

Effect of subthreshold infrared laser treatment for drusen regression on macular autofluorescence in patients with age-related macular degeneration.

BACKGROUND: Subthreshold laser therapy has been shown to cause drusen reduction. Using this method, visible laser burns are not created in the retina; presumably, the energy is absorbed by the retinal pigment epithelium (RPE) and stimulates reabsorption of drusen material, sparing photoreceptors from destruction. We hypothesized that autofluorescence (AF) changes would be visible after such treatment and might be sensitive to quantify RPE changes. METHODS: Twenty eyes of 13 patients with non-exudative age-related macular degeneration were studied. Forty-eight subthreshold infrared diode laser spots were applied as treatment to cause drusen regression. Before, immediately after, and 3 months after treatment, color fundus photography, fluorescein angiography (FA), and autofluorescence (AF) imaging were performed. Treated lesions were identified on overlay images of all three imaging methods. RESULTS: : The averaged sensitivity of AF imaging compared with FA was 29.6+/-28.7% versus 10.2+/-12.2% (P=0.008) at the immediate posttreatment time point and 43.5+/-28.7% versus 33.8+/-26.5% (P=0.043) at the 3-month posttreatment time point, respectively. Reduction of drusen at 3 months correlated with the detection sensitivity of AF imaging at the immediate posttreatment time point (P=0.022). CONCLUSION: Immediately after subthreshold laser treatment, AF imaging was more sensitive to detect RPE changes than FA. This suggests that noninvasive AF imaging may allow prediction of the effect of subthreshold laser treatment and might be used to titrate treatment dose.

Characterization of a novel intraocular drug-delivery system using crystalline lipid antiviral prodrugs of ganciclovir and cyclic cidofovir.

PURPOSE: In an earlier study, a novel intraocular drug-delivery system was reported in which hexadecyloxypropyl-phospho-ganciclovir (HDP-P-GCV) was used as a prototype. The hypothesis was that many biologically effective compounds could be modified to crystalline lipid prodrugs and could be delivered directly into the vitreous in a long-lasting, slow-release form. This study was undertaken to characterize this new drug-delivery system further, by using small particles of HDP-P-GCV and hexadecyloxypropyl-cyclic cidofovir (HDP-cCDV). METHODS: HDP-P-GCV was microfluidized into 4.4-microm (median) particles, injected into rabbit vitreous. The vitreous drug level was then measured at different time points. Crystalline HDP-cCDV was synthesized, suspended in 5% dextrose, and injected into the rabbit's vitreous at 10, 55, 100, 550, or 1000 microg in 50 microL vehicle per eye, to determine the highest nontoxic dose. The dose, 100 microg, was injected into 24 rabbit eyes, to evaluate pharmacokinetics; into 14 rabbit eyes with established HSV retinitis, to evaluate its efficacy; and into 58 rabbit eyes before herpes simplex virus (HSV) infection to evaluate its intraocular antiviral duration. RESULTS: Microfluidized particles of HDP-P-GCV showed an increased drug release rate compared with the large-particle drug formulation, with area under concentration-time curve (AUC) of 219.8 +/- 114.1 (n=3) versus 108.3 +/- 47.2 (n=3) for unmodified HDP-P-GCV during the 12-week period after a 2.8-micromole intravitreal injection. There was a 103% increase of the drug released from the microfluidized formulation of HDP-P-GCV versus the unmodified formulation. Intravitreal injections of HDP-cCDV at doses of 100 microg/eye or lower were not toxic. After the 100 microg/eye injections, HPLC analysis showed a vitreous HDP-cCDV level of 0.05 microM at week 5, which declined to 0.002 microM at week 8. The concentration at week 8 (0.002 microM) remained above the IC50 for cytomegalovirus (0.0003 microM). The pretreatment study demonstrated an antiviral effect that lasted 100 days after a single intravitreal injection. CONCLUSIONS: This crystalline lipid prodrug intravitreal delivery system is an effective approach to achieving sustained, therapeutic drug levels in the eye. Small microfluidized particles of HDP-P-GCV provide more rapid dissolution and higher vitreous drug levels.

Foveal sensitivity and fixation stability before and after macular translocation with 360-degree retinotomy.

PURPOSE: To evaluate the functional changes of the fovea by scanning laser ophthalmoscopy (SLO) fundus perimetry after macular translocation with 360-degree retinotomy, and to determine whether the preoperative macular function estimated by the sensitivity of the fovea and the stability of fixation can predict visual acuity after the surgery. METHODS: Macular translocation with 360-degree retinotomy and simultaneous torsional muscle surgery were performed on 25 eyes of 25 patients with choroidal neovascularization. The index of foveal sensitivity (Isens) and the index of fixation stability (Ifix) before and after surgery were calculated from the microperimetric data. The preoperative Isens and Ifix were compared with postoperative Isens and Ifix, respectively. The correlations of preoperative Isens and Ifix with the visual acuity after the translocation surgery (VApost) were calculated. RESULTS: Isens increased in 14 (56%) of 25 eyes. Ifix improved in 10 (40%) of 25 eyes. The preoperative Isens and VApost were moderately correlated (r = 0.434, P = 0.0295), while the preoperative Ifix and VApost were highly correlated (r = - 0.530, P = 0.0057). CONCLUSION: An increase in foveal sensitivity and an improvement in the fixation stability were demonstrated quantitatively by microperimetry. The preoperative foveal sensitivity and fixation stability were correlated with the postoperative visual acuity. Microperimetry using SLO can be used to investigate foveal function before and after the translocation and to predict the postoperative visual acuity.

Valganciclovir therapy for immune recovery uveitis complicated by macular edema.

PURPOSE: To determine whether treatment with valganciclovir will improve visual acuity in eyes with immune recovery uveitis complicated by macular edema. DESIGN: Prospective open label controlled Phase II drug study. METHODS: Five patients with chronic macular edema as a result of immune recovery uveitis were studied. Baseline fluorescein angiograms, best-corrected ETDRS visions, and cytomegalovirus (CMV) lymphoproliferative T-cell function assays were obtained and repeated after three months of valganciclovir therapy (900 mg daily) and again three months after withdrawal of therapy. RESULTS: Vision improved by a mean of 11 letters in the treatment phase (P =.05). Graded angiograms showed three patients had treatment reduction of macular edema. One patient had rebound increase in macular edema after the withdrawal phase. The CMV lymphoproliferative response was not affected by the valganciclovir. CONCLUSION: Results suggest valganciclovir treatment may benefit visual acuity in patients with macular edema from immune recovery uveitis.

Inhibition of choroidal neovascularization in rats by the urokinase-derived peptide A6.

PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide A6 on laser-induced choroidal neovascularization (CNV). METHODS: In the first arm of the study, subcutaneous injection of A6 (200 mg/kg per day) into the right eyes in 20 rats and phosphate-buffered saline in 20 control rats was started 1 day before laser injury. Angiography was performed at week 2. To evaluate the dose response, a second arm of the study was performed in the left eyes. Half of the treatment group was treated with 400 mg/kg per day, and the remaining half continued to receive 200 mg/kg per day beginning on week 4. Laser injury was made at week 5 and angiography was performed at week 7. Angiographic evaluation, histopathologic evaluation including maximum CNV thickness and factor-VIII-stained endothelium counting were performed in the second arm of the study. Choroidal concentrations of A6 were measured. RESULTS: In the first arm of the study, angiography showed a 40.8% reduction in CNV in the 200-mg/kg per day treatment group, compared with the control (P = 0.0008). In the second arm of the study, angiographic reduction in CNV was 37.9% in the 200-mg/kg per day group (P = 0.0314) and 70.0% in the 400-mg/kg per day group (P = 0.0124), compared with the control. CNV was significantly less in the 400-mg/kg per day group than in the 200-mg/kg per day group (P = 0.0393). Both CNV thickness and number of endothelial cells were reduced in a dose-dependent manner and significantly less than in the control (P < 0.05). Mean choroidal concentration of A6 2 hours after injection was 0.72 micro M in the 200-mg/kg per day (100 mg/kg every 12 hours) and 1.75 micro M in the 400-mg/kg per day (200 mg/kg every 12 hours) treatment groups. Levels at 11 hours after injections were undetectable. CONCLUSIONS: A6 demonstrated antiangiogenic properties in a rat model of CNV and may be useful in the treatment of CNV.

Intraocular properties of urokinase-derived antiangiogenic A6 peptide in rabbits.

To investigate the intraocular properties of an antiangiogenic peptide, A6, a total of 70 New Zealand rabbit eyes were used. For the toxicity study, 0.05 mL of 0.459 M or 0.148 M A6 was injected intravitreally; right eyes received A6, and left eyes received a vehicle. Serial intraocular pressure measurement, slit lamp, and indirect ophthalmoscopy were performed. The rabbit eyes were evaluated by fluorescein angiography, electroretinography, and histology after the scheduled sacrifice. The pharmacokinetics of an intravitreal A6 (0.05 mL of 0.488 M) and a subtenon A6 (0.5 mL of 0.305 M) injection was studied. There was no toxicity observed following the 0.148 M A6 intravitreal injections. In 2 eyes with a 0.459 M A6 intravitreal injection, focal retinal pigmentary change was observed at the injection site, which was contacted by the hyperosmolar drug bolus. Choroidal A6, following the intravitreal injection, remained therapeutic (>or=10 microM) for 72 hours. The vitreous half-life was 19.4 hours. Choroidal concentrations following the subtenon injection were minimal. The low choroidal concentrations observed may relate to the polar nature of A6. More hydrophobic analogs of A6 are likely to cross the retina more efficiently. However, in diseased eyes, in the area of choroidal neovascularization (CNV), the fluid-filled, damaged, edematous retina may permit the drug to enter the choroid in higher concentrations.