Faculty Bibliography

BACKGROUND: Age-related macular degeneration (ARMD) is the most prevalent cause of visual loss in patients older than 60 years in the United States. Observation of drusen is the hallmark finding in the clinical evaluation of ARMD. OBJECTIVES: To segment and quantify drusen found in patients with ARMD using image analysis and to compare the efficacy of image analysis segmentation with that of stereoscopic manual grading of drusen. DESIGN: Retrospective study. SETTING: University referral center.Patients Photographs were randomly selected from an available database of patients with known ARMD in the ongoing Columbia University Macular Genetics Study. All patients were white and older than 60 years. INTERVENTIONS: Twenty images from 17 patients were selected as representative of common manifestations of drusen. Image preprocessing included automated color balancing and, where necessary, manual segmentation of confounding lesions such as geographic atrophy (3 images). The operator then chose among 3 automated processing options suggested by predominant drusen type. Automated processing consisted of elimination of background variability by a mathematical model and subsequent histogram-based threshold selection. A retinal specialist using a graphic tablet while viewing stereo pairs constructed digital drusen drawings for each image. MAIN OUTCOME MEASURES: The sensitivity and specificity of drusen segmentation using the automated method with respect to manual stereoscopic drusen drawings were calculated on a rigorous pixel-by-pixel basis. RESULTS: The median sensitivity and specificity of automated segmentation were 70% and 81%, respectively. After preprocessing and option choice, reproducibility of automated drusen segmentation was necessarily 100%. CONCLUSIONS: Automated drusen segmentation can be reliably performed on digital fundus photographs and result in successful quantification of drusen in a more precise manner than is traditionally possible with manual stereoscopic grading of drusen. With only minor preprocessing requirements, this automated detection technique may dramatically improve our ability to monitor drusen in ARMD

Oxygen is believed to be one of the potential causative agents for the development of nuclear cataract following vitrectomy. The aim of this study was to determine the partial pressure of oxygen (pO2) in different compartments of the rabbit eye, and to describe the changes following vitrectomy. Twenty-six rabbits (3.5-5.3 kg) were anesthetized and oxygen tension was probed using a fiber-optic oxygen sensor system (optode). A micromanipulator was employed to ascertain the exact position of the probe within the eye. Measurements were taken pre- and post-vitrectomy at several defined positions within the vitreous, the lens and the anterior chamber. Follow-up measurements were performed 2 and 8 weeks after vitrectomy. The contralateral eye served as a control. Measurements in the normal rabbit eye showed that oxygen tension in the globe is asymmetrical with the lowest pO2 in the nucleus of the lens (10.4 mmHg+/-3.0). The region of the lens near the posterior capsule has an oxygen tension close to the values of the vitreous directly behind the posterior capsule (12.4 mmHg+/-3.1). The highest pO2 within the posterior compartment of the eye was measured close to the retinal surface (40-l60 mmHg) depending on neighboring large vessels. The tension drops off rapidly to 20 mmHg some 0.5 mm from the retina. From that position to the posterior surface of the lens there is a shallow gradient of decreasing pO2. Immediately following vitrectomy the pO2 in the BSS replacement varied from ca. 90-140 mmHg, and decreased over approximately 30 min. to levels that were 2-3 times that of normal vitreous. Two weeks after vitrectomy the pO2 values in the lens were 2-3 times as high as in the control eye (p < 0.05). In addition there is no longer a gradient in the vitreous cavity, except close to the retina. Eight weeks after vitrectomy, pO2 levels in the lens were decreased but still remained higher than in the normal eye (13.83 mmHg+/-0.02). The pO2 gradient in the vitreous was not detectable anymore. Overall the results provide evidence that oxygen levels in the lens increase significantly after vitrectomy in rabbits. If this occurs in humans it may contribute to cataract formation following surgery.

PURPOSE: Screening for detection of retinopathy of prematurity (ROP) currently is limited to indirect ophthalmoscopy, which requires considerable examiner skill and experience. We investigated whether conventional 10 MHz B-scan ultrasonography could document the clinical stages of ROP as accurately as indirect ophthalmoscopy. METHODS: Thirty-four eyes of 18 neonates were examined by masked, independent observers with indirect ophthalmoscopy and digitally recorded 10-MHz B-scan ultrasonography. After pupil dilation and lid speculum placement, the retinologist recorded the stage of retinopathy with a retinal drawing. The ultrasonographer, without use of papillary mydriatics or lid speculum, determined the presence or absence of a ridge or tractional elements, if present on the ridge. RESULTS: Ultrasound grade correlated with clinical grade (R = .79, P < .001). However, nine eyes were overdiagnosed by one stage, and one eye, in which a peripheral detachment was mistaken for an artifact, was underdiagnosed. CONCLUSIONS: Ten-megahertz ultrasonography offers the potential of imaging and detecting the clinical stages of ROP; the use of higher ultrasound frequencies, now becoming commercially available, is likely to enhance diagnostic accuracy. Care must be taken to distinguish between artifact and true anatomical structures in noncontact ultrasound examinations. Neonates with suspected ROP could be screened with B-scan ultrasonography by neonatal personnel without pupillary dilatation or lid speculum, thus eliminating potential morbidity, and clinically significant cases of ROP then could be referred to the retinologist.

PURPOSE: The aim of this study was to describe the clinical and angiographic response of squamous cell carcinoma (SCC) of the conjunctiva to treatment with photodynamic therapy (PDT). DESIGN: Interventional case series. METHODS: In a prospective study, three patients (62 to 86 years old) with SCC of the conjunctiva were treated with PDT. Patients received one to three treatments of verteporfin (6 mg/m(2) body surface area, intravenously). The light dose was calculated as 50 J/cm(2). All tumors were irradiated 1 minute after injection. The mean follow-up time was 8.6 months (7 to 12 months). Main outcome measurements were clinical and angiographic response and treatment-related side effects. RESULTS: One week after treatment, angiographic occlusion of tumor vasculature and normal conjunctival vessels was observed in all patients. Tumor regression was noted in all patients 1 month after treatment. Two patients had complete regression (clinical and angiographic observation) after one or two treatments for the entire follow-up time. One tumor involved large aspects of the conjunctiva and cornea. In this case, only the treated areas showed tumor regression. PDT caused minimal temporary local irritation in two patients, and small conjunctival hemorrhages and mild transient chemosis in the three eyes directly after treatment. One patient had infusion-related back pain. CONCLUSION: The preliminary results of this study suggest that PDT may be a valuable addition to the treatment of patients with SCC of the conjunctiva. However, longer follow-up is necessary to assess the duration and degree of tumor control.

Normal macular photographic patterns are geometrically described and mathematically modeled. Forty normal color fundus photographs were digitized. The green channel gray-level data were filtered and contrast enhanced, then analyzed for concentricity, convexity, and radial resolution. The foveal data for five images were fit with elliptic quadratic polynomials in two zones: a central ellipse and a surrounding annulus. The ability of the model to reconstruct the entire foveal data from selected pixel values was tested. The gray-level patterns were nested sets of concentric ellipses. Gray levels increased radially, with retinal vessels changing the patterns to star shaped in the peripheral fovea. The elliptic polynomial model could fit a high-resolution green channel foveal image with mean absolute errors of 6.1% of the gray-level range. Foveal images were reconstructed from small numbers of selected pixel values with mean errors of 7.2%. Digital analysis of normal fundus photographs shows finely resolved concentric elliptical foveal and star-shaped parafoveal patterns, which are consistent with anatomical structures. A two-zone elliptic quadratic polynomial model can approximate foveal data, and can also reconstruct it from small subsets, allowing improved macular image analysis

OBJECTIVE: To describe fluorescein angiographic guidelines for the use of verteporfin therapy in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) or other conditions based on 2-year vision outcomes from the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Investigation and Verteporfin in Photodynamic Therapy (VIP) Trial. METHODS: Three multicenter, double-masked, placebo-controlled randomized clinical trials at 28 ophthalmology clinical centers in Europe and North America involving prospectively identified patients with best-corrected visual acuity (Snellen equivalent) of approximately 20/20 to 20/200, subfoveal CNV secondary to AMD or pathologic myopia with evidence of CNV, and a lesion greatest linear dimension of 5400 micro m or less. Fluorescein angiography was to be performed on all patients at enrollment and at regular 3-month follow-up visits through 2 years. The initial treatment laser spot size and all subsequent treatment decisions were based on the investigator's interpretation of these fluorescein angiograms. Photographic materials forwarded to the Wilmer Photograph Reading Center were reviewed by masked graders. MAIN OUTCOME MEASURES: Baseline angiographic features, including lesion composition and size, morphologic response to treatment during follow-up (eg, absence of leakage), and reliability (kappa values) of grading selected characteristics based on a 10% regrading of baseline visits. RESULTS: Terms and examples of different lesions and lesion components are provided to assist recognition of fluorescein angiographic characteristics of choroidal neovascular lesions that were important in determining when and where to apply verteporfin therapy. The kappa statistics for agreement of identification of lesion characteristics by the Wilmer Photograph Reading Center for these trials ranged from 0.70 to 0.85. CONCLUSIONS: Ophthalmologists should consider interpreting fluorescein angiographic images of subfoveal lesions with terms provided to follow recommendations regarding which patients are most likely to benefit from verteporfin therapy based on results from the TAP Investigation and VIP Trial.

PURPOSE: To InternetAdvance publication at ajo.com Feb 26, 2002. investigate the effect of photodynamic therapy using verteporfin on choroidal melanoma. DESIGN: Interventional case series. METHOD: Four patients with choroidal melanoma who showed recurrence or no response after previous brachytherapy and transpupillary thermotherapy were treated with photodynamic therapy. RESULTS: One tumor decreased in size and remained stable for 18 months. One tumor had no growth for 11 months. Two melanomas continued to grow, necessitating enucleation. CONCLUSIONS: Of the four eyes that had failed conventional therapies, two would have been salvaged (to date) with photodynamic therapy. However, additional studies are needed to determine if photodynamic therapy can play a role in the management of choroidal melanoma.

PURPOSE: To investigate the correlation between reading speed and scotoma size in patients with subfoveal occult with no classic choroidal neovascularization (CNV) in age-related macular degeneration (AMD) participating at 2 of 28 centers in the Verteporfin in Photodynamic Therapy trial. DESIGN: Prospective, observational case series. PARTICIPANTS: Twenty-two eyes of 22 patients with occult with no classic CNV in AMD. METHODS: Patients' reading speed was examined using a German-language reading test (Radner Lesetest). Scotoma size was measured using the microperimetry program 2.01 of the Rodenstock Scanning Laser Ophthalmoscope. MAIN OUTCOME MEASURES: Reading acuity, reading speed, size of absolute (AS) and relative scotoma (RS). RESULTS: There was a significant correlation between the size of AS and reading speed (r = -0.48, P = 0.023), as well as AS and reading acuity (r = 0.52, P = 0.013). No correlation was seen between RS and reading speed or reading capacity. CONCLUSION: The size of absolute scotoma correlated significantly with reading capacity and reading speed and may influence these measures.

BACKGROUND: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. METHODS: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 microm and 3000 microm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). RESULTS: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. CONCLUSIONS: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research