Optical coherence tomography homography for detection of retinal displacement: a validation study.

PURPOSE: Retinal displacement following rhegmatogenous retinal detachment (RRD) has been associated with inferior functional outcomes. Recent evidence using an overlay technique suggests that fundus-autofluorescence underestimates post-RRD repair retinal displacement. This study aims to validate the overlay technique in normal eyes and to determine its sensitivity and specificity at detecting retinal displacement. METHODS: We conducted a retrospective case series involving 66 normal eyes, each with at least two separate infrared (IR) images at different time points. Overlay of the two images was based on manual marking of choroidal and optic nerve head (ONH) landmarks. For each set of two IR images, computer code for homography generated two outputs, flipping view video and an overlay picture. First, validation of choroidal/ONH alignment was performed using the flipping view video to ensure accurate manual markings. Then, two different masked graders (AB + IM) evaluated the overlays for presence of retinal displacement. 16 control eyes following RRD repair with detected retinal displacement on FAF imaging assessed sensitivity and specificity of the technique. RESULTS: 94% of overlays were found to be well aligned (62/66). 11 cases exhibited errors on flipping view analysis (choroidal/ONH misalignment). Those 11 cases had a significantly higher rate of retinal displacement (false positives) compared to cases without errors (8/11,72% Vs 54/55,98%,P = 0.001). Sensitivity and specificity of the overlay technique for detecting retinal displacement considering only adequate flipping view cases (n = 55) were calculated as 100% and 98%, respectively. CONCLUSIONS: IR overlay emerges as a reliable and valid method for detecting retinal displacement, exhibiting excellent sensitivity and specificity.

Rapid, Accurate, Ranking of Protein-Ligand Binding Affinities with VM2, the Second-Generation Mining Minima Method.

The structure-based technologies most widely used to rank the affinities of candidate small molecule drugs for proteins range from faster but less reliable docking methods to slower but more accurate explicit solvent free energy methods. In recent years, we have advanced another technology, which is called mining minima because it "mines" out the main contributions to the chemical potentials of the free and bound molecular species by identifying and characterizing their main local energy minima. The present study provides systematic benchmarks of the accuracy and computational speed of mining minima, as implemented in the VeraChem Mining Minima Generation 2 (VM2) code, across two well-regarded protein-ligand benchmark data sets, for which there are already benchmark data for docking, free energy, and other computational methods. A core result is that VM2's accuracy approaches that of explicit solvent free energy methods at a far lower computational cost. In finer-grained analyses, we also examine the influence of various run settings, such as the treatment of crystallographic water molecules, on the accuracy, and define the costs in time and dollars of representative runs on Amazon Web Services (AWS) compute instances with various CPU and GPU combinations. We also use the benchmark data to determine the importance of VM2's correction from generalized Born to finite-difference Poisson-Boltzmann results for each energy well and find that this correction affords a remarkably consistent improvement in accuracy at a modest computational cost. The present results establish VM2 as a distinctive technology for early-stage drug discovery, which provides a strong combination of efficiency and predictivity.

Effect of Music Selection on Anxiety Level during Intravitreal Injections for Individuals of Varying Cultures.

PURPOSE: To investigate music selection as a treatment for anxiety during Intravitreal injections (IVI) for individuals of varying cultures. METHODS: 106 individuals were enrolled in this randomized controlled study. Individuals were randomized into one to three categories: (1) a control group in which the IVI procedure was performed without music (n = 35), (2) an experimental group in which the music was selected by the physician (n = 36), (3) an experimental group in which the music was selected by the patient (n = 35). After the procedure, all patients responded to a questionnaire regarding their level of experienced anxiety, pain and discomfort (grade 0-10). The primary outcome was anxiety level during the procedure. RESULTS: The experimental group in which patients selected music had higher number of patients with low anxiety score compared to the other groups (anxiety score <4 in 19,18 and 27 patients, respectively, p = .04). Interestingly, patients who answered the questionnaire in Arabic were less likely to desire music on subsequent injections compared to Hebrew and English speakers (52% Vs 78% Vs 100%, p = .02). Music was deemed by both experimental groups as an effective method to induce relaxation (average score of 6.6 and 7.2 in group 2 and 3, respectively). Preference for music on subsequent injections was increased in both experimental groups compared to the control group (P < .01). Patients in the third group preferred music selection on future injections more than the other groups (P < .01). CONCLUSION: Music selection may be an effective way to reduce anxiety levels during IVI. Preference for music during future injections is higher in patients who were exposed to music during IVI and may be influenced by culture.

Fabrication and characterization methods for investigating cell-matrix interactions in environments possessing spatial orientation heterogeneity.

Fibrillar collagen is a ubiquitous structural protein that plays a significant role in determining the mechanical properties of various tissues. The constituent collagen architecture can give direct insight into the respective functional role of the tissue due to the strong structure-function relationship that is exhibited. In such tissues, matrix structure can vary across local subregions contributing to mechanical heterogeneity which can be implicated in tissue function or failure. The post-myocardial infarction scar environment is an example of note where mechanically insufficient collagen can result in impaired cardiac function and possibly tissue rupture due to post-MI cellular response and matrix interactions. In order to further develop the understanding of cell-matrix interactions within heterogeneous environments, we developed a method of heterogeneous collagen gel fabrication which produces a region of randomly oriented fibers directly adjacent to an interconnected region of anisotropic alignment. To fully capture and evaluate the degree of alignment and spatial orientation heterogeneity, several image processing and automated analysis methods were employed. Our analysis revealed the successful fabrication of an interconnected spatially heterogeneous collagen gel possessing distinct regions of random or preferential alignment. Additionally, embedded cell populations were observed to recognize and reorient with their underlying and surrounding architectures through our cell-centric analysis techniques. STATEMENT OF SIGNIFICANCE: Fibrillar collagen is a structural protein that contributes to the architecture-function relationship exhibited by various tissues where mechanically insufficient collagen architecture can lead to tissue failure. One environment where this can occur is the post-myocardial infarction scar environment where too much or too little collagen accumulation coupled with spatial fiber orientation heterogeneity can lead to environments incapable of normal mechanical functionality. While there are methodologies capable of generating aligned constructs, they do so with varying degrees of control and complexity with many producing uniform construct alignment. The presented platform is simple and produces continuous constructs possessing inherent spatial orientation heterogeneity. Coupling this with image processing and automated analysis methods enables the probing of fundamental cell-matrix interactions within heterogeneous environments.

Enhanced depth imaging in swept-source optical coherence tomography: Improving visibility of choroid and sclera, a masked study.

PURPOSE: To compare enhanced depth imaging in swept-source optical coherence tomography and non-enhanced depth imaging optical coherence tomography in their ability to capture choroidal and scleral details. METHODS: Averaged foveal B-Scans were obtained from 40 eyes of 20 healthy volunteers by swept-source optical coherence tomography with and without enhanced depth imaging. Visibility and contrast of vascular details within the choroid, choroidoscleral junction, and sclera were evaluated by masked readers using an ordinal scoring scale. Outcomes were analyzed using the Wilcoxon signed rank-sum test. RESULTS: Visibility of the choroidal vascular details (Z = 5.94, p < .001), the choroidoscleral junction (Z = 5.85, p < .001), and the sclera (Z = 6.80, p < .001) was significantly higher with enhanced depth imaging than with non-enhanced depth imaging swept-source optical coherence tomography. Similarly, image contrast was significantly higher with enhanced depth imaging than with non-enhanced depth imaging swept-source optical coherence tomography for the choroidal vascular details (Z = 9.47, p < .001), for the choroidoscleral junction (Z = 9.28, p < .001), and for the sclera (Z = 9.42, p < .001). CONCLUSION: Enhanced depth imaging applied to swept-source optical coherence tomography-averaged foveal B-scans enhances visualization of the choroidal details, of the choroidoscleral junction, and of the sclera. This novel modality can easily be implemented in clinics and could improve our understanding of conditions involving the choroid or the sclera.

Insights from free-energy calculations: protein conformational equilibrium, driving forces, and ligand-binding modes.

Accurate free-energy calculations provide mechanistic insights into molecular recognition and conformational equilibrium. In this work, we performed free-energy calculations to study the thermodynamic properties of different states of molecular systems in their equilibrium basin, and obtained accurate absolute binding free-energy calculations for protein-ligand binding using a newly developed M2 algorithm. We used a range of Asp-Phe-Gly (DFG)-in/out p38α mitogen-activated protein kinase inhibitors as our test cases. We also focused on the flexible DFG motif, which is closely connected to kinase activation and inhibitor binding. Our calculations explain the coexistence of DFG-in and DFG-out states of the loop and reveal different components (e.g., configurational entropy and enthalpy) that stabilize the apo p38α conformations. To study novel ligand-binding modes and the key driving forces behind them, we computed the absolute binding free energies of 30 p38α inhibitors, including analogs with unavailable experimental structures. The calculations revealed multiple stable, complex conformations and changes in p38α and inhibitor conformations, as well as balance in several energetic terms and configurational entropy loss. The results provide relevant physics that can aid in designing inhibitors and understanding protein conformational equilibrium. Our approach is fast for use with proteins that contain flexible regions for structure-based drug design.

Patient preferences for diabetic retinopathy health States.

PURPOSE. To develop standardized descriptions of health states that characterize vision-specific functional impacts of diabetic retinopathy (DR) according to levels of visual acuity and contrast sensitivity and to elicit preferences for these health states from persons with DR and assign weighted values to them. METHODS. Vision-specific descriptions of health states were developed based on a literature review and patient and physician interviews. The content was based on items from the National Eye Institute Visual Functioning Questionnaire (VFQ) and reflected functional impacts experienced by DR patients. Values were assigned to the range of health states, anchored by the extremes full vision and death, by using the time-tradeoff method in a sample of 98 Canadian DR patients from three clinical centers. RESULTS. The mean age of the sample was 60.4 years, and 56% were men. Mean preferences decreased from 0.98 (better-eye logMAR [Snellen equivalent] acuity, > or =20/40; worse-eye Snellen equivalent, > or =20/200) to 0.67 (Snellen equivalent visual acuity, < or =20/200, contrast sensitivity, < or =21 letters bilaterally). Preferences decreased with increasing severity of functional deficits and did not vary significantly by sex, age, VFQ quartile, or better- or worse-eye acuity. CONCLUSIONS. This is the first study that has been conducted to estimate preferences for standardized DR-specific health states, accounting for visual acuity and contrast sensitivity in both eyes. The results showed that the development and progression of DR are associated with substantial declines in preferences. In addition to the progressively greater impact from declining ETDRS visual acuity and contrast sensitivity, preference weights declined with increasing bilateral disparity. These preference values are useful for comparing the cost effectiveness of ophthalmic treatments.

Modeling Protein-Ligand Binding by Mining Minima.

We present the first application of the mining minima algorithm to protein-small molecule binding. This end-point approach use an empirical force field and implicit solvent models, treats the protein binding-site as fully flexible and estimates free energies as sums over local energy wells. The calculations are found to yield encouraging agreement with experiment for three sets of HIV-1protease inhibitors and a set of phosphodiesterase 10a inhibitors. The contributions of various aspects of the model to its accuracy are examined, and the Poisson-Boltzmann correction is found to be the most critical. Interestingly, the computed changes in configurational entropy upon binding fall roughly along the same entropy-energy correlation previously observed for smaller host-guest systems. Strengths and weaknesses of the method are discussed, as are the prospects for enhancing accuracy and speed.

Experimental evaluation of a bovine pericardium-derived collagen matrix buttress in ileocolic and colon anastomoses.

BACKGROUND: Anastomotic leakage is a major complication of colorectal surgery. The purpose of this study was to evaluate and compare stapled ileocolic and colon-colon anastomoses with or without a collagen buttress derived from bovine pericardium in the immediate postoperative period. METHODS: Various stapling devices were used to create ileocolic and colon-colon anastomoses in a canine model. Ileocolic anastomoses were created by simulating two different techniques: "open" and "laparoscopic". Colon-colon anastomoses were created by using a double-stapled technique. A total of 27 colon anastomoses (13 left colon-colon, 8 right "laparoscopic", and 6 right "open") were created. Anastomoses buttressed with bovine pericardium (n = 15) were compared to anastomoses without any reinforcement (n = 12). Staple lines were evaluated 4 hours after operation. Evaluation included bursting pressure and bursting location. RESULTS: No stapler device malfunction occurred. Excision rings were complete in all colon-colon anastomoses. All non-buttressed anastomoses burst at the staple line, whereas with buttressed anastomoses the adjacent intestine burst (p = 0.0001). The intestinal bursting pressure of bowel segments with buttressed staple lines (mean, 362 mmHg) was significantly higher than the bursting pressure of non-buttressed staple lines (mean, 204 mmHg, p < 0.0001). CONCLUSION: The use of a collagen matrix buttress derived from bovine pericardium in stapled ileocolic and colon-colon anastomoses was safe. Buttressed anastomoses showed greater bursting strength as compared to non-buttressed anastomoses in the immediate postoperative period in a canine model.

Older women with age-related macular degeneration have a greater risk of falls: a physiological profile assessment study.

OBJECTIVES: To determine whether older women with exudative age-related macular degeneration (AMD) are at greater risk of falls. DESIGN: Cross-sectional study. SETTING: A hospital-based ophthalmology clinic in Vancouver, Canada. PARTICIPANTS: One hundred fifteen older (aged > or = 70) community-dwelling women with exudative AMD (AMD cohort) and two control groups: 54 community-dwelling women without exudative AMD drawn from the same community (non-AMD cohort) and 341 community-dwelling Australian women (Australian normative cohort). MEASUREMENTS: Participants were assessed for falls risk using the short-form Physiological Profile Assessment (PPA), which provides a fall risk index score and subcomponent measures of vision, proprioception, strength, reaction time, and postural sway. RESULTS: The mean fall risk index score in the AMD cohort (3.20) was significantly greater than that of the non-AMD cohort (1.21; P<.001), and fall risk scores increased with age to a greater extent in the AMD cohort. The higher fall risk scores in the AMD cohort resulted from significantly worse performance on each PPA test, not just the test of vision. The AMD cohort also performed worse than the Australian normative cohort in tests of vision, reaction time, and postural sway. CONCLUSION: Older women with AMD have impaired balance, slow visual reaction times, and poor vision, which in combination result in a significantly greater risk of falls than population norms. These deficits are clearly indicated in the physiological falls profile for the group. Strategies to enhance balance may be particularly beneficial to prevent falls in this group.

Recurrence of choroidal neovascularisation after photodynamic therapy in patients with age-related macular degeneration.

AIM: To determine the incidence of recurrence of choroidal neovascularisation (CNV) 18 months after cessation of photodynamic therapy (PDT) with verteporfin monotherapy in patients with age-related macular degeneration (AMD). METHODS: This was a prospective interventional cohort study. The sample consisted of 108 individuals with CNV secondary to AMD which was treated with PDT. Data on demographics, pre-PDT and post-PDT Early Treatment of Diabetic Retinopathy Study (ETDRS) acuity, pre-PDT lesion size and composition were collected for each participant. All participants returned for fundus photographs and ETDRS acuity measurements 18 months after their final PDT, which were compared with the same measurements from the final treatment session to determine recurrence status. Recurrences were classified primarily on the basis of haemorrhage and increased lesion size. RESULTS: Recurrences were observed in 36 of 108 (33%) eyes. 23 of 36 (64%) recurrences were clinically meaningful. Of the explanatory variables considered, only final PDT acuity was significantly different between those that recurred (45.5 ETDRS letters) and those that did not (38.4 letters; p = 0.03). CONCLUSION: CNV recurrences are common after PDT for AMD, occurring in 33% of eyes in this study. Visual acuity measured at the final PDT treatment visit may be a predictor of subsequent recurrence.

Photodynamic therapy for subretinal neovascularization in type 2A idiopathic juxtafoveolar telangiectasis.

BACKGROUND: Photodynamic therapy (PDT) with verteporfin is now the standard of care worldwide for the treatment of choroidal neovascularization, but has been used only rarely in those with subretinal neovascular membranes (SRNVM) due to type 2A idiopathic juxtafoveolar retinal telangiectasis (IJT). We performed a retrospective study to examine the outcome of patients treated with PDT for SRNVM secondary to IJT. METHODS: Retrospective interventional case series of 7 eyes of 6 IJT patients with SRNVMs treated with PDT. Ophthalmic examination and fluorescein angiography were performed before treatment, with retreatment every 3 months as needed. The main outcome was the proportion of patients avoiding vision loss (change of +/- 4 letters, or better). RESULTS: Baseline Snellen acuity ranged from 20/40 to 20/400 (median 20/80). Mean follow-up was 21 months. Patients received 2.4 treatments on average. Five of 7 patients avoided vision loss; acuity improved in 3 eyes (> or = 1 line improvement), stayed the same in 2 eyes (+/- 4 letters) and decreased in 2 eyes (> or = 1 line decrease) over time. Median final acuity was 20/80. Five of 7 eyes had final acuities of > or = 20/200. No leakage was observed in any eyes following cessation of treatment.

Combined photodynamic therapy and intravitreal triamcinolone for the treatment of myopic choroidal neovascularization in a 13-year-old girl.

BACKGROUND: Combination photodynamic therapy with verteporfin (PDT) and intravitreal triamcinolone acetonide (IVT) is currently being investigated as a treatment for choroidal neovascularization (CNV) due to age-related macular degeneration. However, PDT with triamcinolone has never previously been described in the treatment of CNV secondary to pathologic myopia, or in a young person. We describe the case of a young girl treated with combination PDT and IVT for a myopic subfoveal CNV membrane. METHODS: This study was an interventional case report. The medical chart of a 13-year-old child treated with combination PDT with IVT was reviewed for changes in visual acuity on the ETDRS chart, CNV leakage on fluorescein angiography, and adverse events reported. RESULTS: ETDRS visual acuity improved from 20/80-2 to 20/25 in the right eye over 7 months following two treatments of a myopic CNV lesion with combination PDT and IVT. Following treatment, an inactive scar with no further leakage was visible on fluorescein angiography. An increase in intraocular pressure was associated with the second IVT treatment, and successfully treated with topical therapy. CONCLUSIONS: Combination PDT with IVT may be considered under appropriate circumstances to treat children with CNV.

One-year outcomes after photodynamic therapy in patients with age-related macular degeneration with poor baseline visual acuity.

BACKGROUND: Photodynamic therapy with verteporfin (PDT) has been demonstrated in randomized controlled trials to be a safe and effective therapy for choroidal neovascular membranes (CNV) secondary to age-related macular degeneration (AMD). Limited information is available on the prognosis with PDT for patients who fell outside the inclusion criteria for the clinical trials, however. The purpose of this study is to describe the clinical course of patients with CNV lesions in AMD treated with PDT, with baseline visual acuities sufficiently poor to warrant exclusion from previous randomized trials. METHODS: Retrospective case series. Ten consecutive patients with CNV secondary to exudative AMD treated with PDT with baseline visual acuity less than 34 ETDRS letters were followed for 1 year. The main outcome was median change in visual acuity on the ETDRS chart. RESULTS: The median change in acuity over 12 months was + 13 letters. All patients lost <3 lines of ETDRS acuity, and eight of ten patients (80%) gained at least one line of vision, over 12 months. CONCLUSIONS: In our series, patients with low visual acuity at baseline appeared to respond to PDT on both visual acuity and fluorescein angiographic measurements. PDT treatment may be considered for selected patients with these baseline characteristics.

Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial.

OBJECTIVE: To compare the treatment effect and safety of photodynamic therapy with verteporfin using a standard (SF) or reduced (RF) light fluence rate with that of placebo therapy in patients with subfoveal minimally classic choroidal neovascularization (CNV) with age-related macular degeneration. DESIGN: Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial. SETTING: Nineteen ophthalmology practices in North America and Europe. PARTICIPANTS: Patients with initial best-corrected visual acuity of at least 20/250 and a lesion size of no greater than 6 Macular Photocoagulation Study (MPS) disc areas. METHODS: We randomly assigned 117 patients (1:1:1) to verteporfin infusion (6 mg/m(2)) and light application with an RF rate (300 mW/cm(2)) for 83 seconds (light dose of 25 J/cm(2)) or an SF rate (600 mW/cm(2)) for 83 seconds (light dose of 50 J/cm(2)) or to placebo infusion with RF or SF. Treatment was repeated every 3 months if the treating physician noted fluorescein leakage from CNV on angiography. Patients in whom a predominantly classic lesion developed could receive open-label standard verteporfin treatment. Best-corrected visual acuity was measured every 3 months, and angiographic changes were assessed by the Photograph Reading Center through the 3-month examination unless an ocular adverse event or conversion to a predominantly classic lesion was identified by an investigator. Safety was assessed throughout the study. All outcomes were on an intent-to-treat basis. RESULTS: One hundred three (88%) of 117 patients completed the 24-month examination. Twelve (30%) of 40 patients assigned to placebo received open-label standard verteporfin treatment after confirmation of presence of predominantly classic CNV. At month 12, a loss of at least 3 lines of visual acuity occurred in 5 (14%) of 36 eyes assigned to RF and 10 (28%) of 36 eyes assigned to SF, compared with 18 (47%) of 38 eyes assigned to placebo (RF, P = .002; SF, P = .08; RF + SF, P = .004). At month 24, this loss occurred in 9 (26%) of 34 eyes assigned to RF and 17 (53%) of 32 assigned to SF, compared with 23 (62%) of 37 eyes assigned to placebo (RF, P = .003; SF, P = .45; RF + SF, P = .03). Progression to predominantly classic CNV by 24 months was more common in the placebo group (11 [28%] of 39 patients compared with 2 [5%] of 38 in the RF group [P = .007] and 1 [3%] of 37 in the SF group [P = .002]). No unexpected ocular or systemic adverse events were identified. Treatment-related, usually transient visual disturbances were 13% with SF, 10% with placebo, and 5% with RF. CONCLUSIONS: Verteporfin therapy safely reduced the risks of losing at least 15 letters (> or =3 lines) of visual acuity and progression to predominantly classic CNV for at least 2 years in individuals with subfoveal minimally classic lesions due to age-related macular degeneration measuring 6 MPS disc areas or less. Based on the overall evidence available on verteporfin therapy for these lesions, the VIM Study Group would consider recommending verteporfin therapy for relatively small minimally classic lesions similar to those enrolled in the VIM Trial.

Clinical findings in a carrier of a new mutation in the choroideremia gene.

OBJECTIVE: To describe the clinical and molecular findings of a female carrier of a new mutation in the choroideremia (CHM) gene. DESIGN: Single interventional case report. METHODS: A 27-year-old woman was seen with mild difficulties with dark adaptation and a history of a retinal degeneration in her father and choroideremia in 3 male paternal first cousins. Visual acuity measurements, peripheral and color vision tests, electroretinography (ERG), Goldmann visual fields, fluorescein angiogram, computed tomography scan, and DNA analysis were performed. MAIN OUTCOME MEASURES: (1) Visual fields, (2) fluorescein angiography, and (3) DNA analysis. RESULTS: Visual acuity decreased from 20/30 to 10/200 in the right eye abruptly over 2 months, then remained stable over 2 years of follow-up and remained 20/25 in the left eye. Goldmann visual fields showed development of a central scotoma in the right eye concurrent with the rapid decline. A small amount of subretinal hemorrhage was visible on dilated fundus examination at that time, but definite leakage was not evident on fluorescein angiography; afterwards, a choroidal neovascular membrane (CNV) was suspected. The ERG was normal. DNA analysis revealed that the patient was heterozygous for a previously undescribed substitution mutation at the 3'-splice site of intron 6 of the CHM gene (850-1 G to C), confirmed by mRNA analysis with reverse transcriptase polymerase chain reaction. CONCLUSIONS: Severe visual acuity loss rarely occurs in female carriers of choroideremia mutations. The diagnosis should be considered in patients with a suitable family history and fundus findings. Physicians should consider the possibility of CNV development in such patients, which may be a response to abnormal retinal pigment epithelium. Recognition of this new mutation may help identify patients who could benefit from current and future treatments to protect against vision loss.

Acute severe visual acuity decrease after photodynamic therapy with verteporfin: case reports from randomized clinical trials-TAP and VIP report no. 3.

PURPOSE: To describe in detail occurrences of acute severe visual acuity decrease after photodynamic therapy (PDT) with verteporfin in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) Investigation and the Verteporfin In Photodynamic therapy (VIP) Trial. DESIGN: Observational case series. METHODS: Retrospective review of all cases that developed acute severe visual acuity decrease after treatment. RESULTS: Of 15 acute severe visual acuity decrease events originally identified in 14 eyes of 14 patients, one event in one patient was judged unlikely to have been an acute severe visual acuity decrease event on retrospective review of these events in preparation of this report. Eleven events occurred after the first treatment. At follow-up, 10 improved by at least 1 line in visual acuity from the level noted at the time of the event. Of the nine patients returning for the month 24 examination, visual acuity decreased at least 3 lines from baseline in six, including at least 6 lines in four, and remained within 1 line in three. Associated abnormal morphology included three with a serous macular detachment and abnormal choroidal hypofluorescence, four with macular hemorrhage, three with a greenish subfoveal hemorrhage, and four with no abnormality. Events appeared to be more likely when patients had a visual acuity of 20/50 or better. CONCLUSIONS: Acute severe visual acuity decrease after PDT with verteporfin was an uncommon event; the risk did not outweigh the benefits of therapy previously reported. When considering verteporfin therapy, patients should be warned of the possibility of this serious adverse event.