Showing papers by "Philip J. Rosenfeld published in 2022"

Automatic geographic atrophy segmentation using optical attenuation in OCT scans with deep learning.

Abstract: A deep learning algorithm was developed to automatically identify, segment, and quantify geographic atrophy (GA) based on optical attenuation coefficients (OACs) calculated from optical coherence tomography (OCT) datasets. Normal eyes and eyes with GA secondary to age-related macular degeneration were imaged with swept-source OCT using 6 × 6 mm scanning patterns. OACs calculated from OCT scans were used to generate customized composite en face OAC images. GA lesions were identified and measured using customized en face sub-retinal pigment epithelium (subRPE) OCT images. Two deep learning models with the same U-Net architecture were trained using OAC images and subRPE OCT images. Model performance was evaluated using DICE similarity coefficients (DSCs). The GA areas were calculated and compared with manual segmentations using Pearson's correlation and Bland-Altman plots. In total, 80 GA eyes and 60 normal eyes were included in this study, out of which, 16 GA eyes and 12 normal eyes were used to test the models. Both models identified GA with 100% sensitivity and specificity on the subject level. With the GA eyes, the model trained with OAC images achieved significantly higher DSCs, stronger correlation to manual results and smaller mean bias than the model trained with subRPE OCT images (0.940 ± 0.032 vs 0.889 ± 0.056, p = 0.03, paired t-test, r = 0.995 vs r = 0.959, mean bias = 0.011 mm vs mean bias = 0.117 mm). In summary, the proposed deep learning model using composite OAC images effectively and accurately identified, segmented, and quantified GA using OCT scans.

Multimodal Imaging and En Face OCT Detection of Calcified Drusen in Eyes with Age-Related Macular Degeneration

Abstract: PurposeEn face OCT imaging was investigated as a method for the detection and monitoring of calcified drusen in eyes with nonexudative age-related macular degeneration (AMD).DesignRetrospective case series of a prospective study.ParticipantsPatients with nonexudative AMD.MethodsA retrospective review was performed of same-day color fundus (CF), fundus autofluorescence (FAF), near-infrared (NIR), and en face swept-source (SS) OCT images to identify eyes with nonexudative AMD and calcified drusen. The appearance and progression of these lesions were compared using the different imaging methods.Main Outcome MeasuresComparison between the presence of calcified drusen observed on CF images with the detection of these lesions on FAF, NIR, and en face SS OCT images.ResultsTwo hundred twenty eyes from 139 patients with nonexudative AMD were studied, with 42.7% of eyes containing calcified drusen either at baseline or during follow-up visits. On the en face SS OCT images, calcified drusen appeared as dark focal lesions referred to as choroidal hypotransmission defects (hypoTDs) that were detected in the choroid using a sub–retinal pigment epithelium (RPE) slab. The corresponding B-scans showed drusen with heterogenous internal reflectivity, hyporeflective cores, and hyperreflective caps. In most calcified drusen, choroidal hypertransmission defects (hyperTDs) were observed to develop over time around the periphery of the hypoTDs, giving them the appearance of a donut lesion on the en face SS OCT images. These donut lesions were associated with significant attenuation of the overlying retina, and the corresponding FAF images showed hypoautofluorescence at the location of these lesions. The donut lesions fulfilled the requirement for a persistent hyperTD, which is synonymous with complete RPE and outer retinal atrophy (cRORA). Six eyes displayed regression of the calcified drusen without cRORA developing. B-scans at the location of these regressed calcified drusen showed deposits along the RPE, with outer retinal thinning in the regions where the calcified lesions previously existed.ConclusionsEn face OCT imaging is a useful method for the detection and monitoring of calcified drusen and can be used to document the evolution of these drusen as they form donut lesions or foci of cRORA. En face OCT imaging was investigated as a method for the detection and monitoring of calcified drusen in eyes with nonexudative age-related macular degeneration (AMD). Retrospective case series of a prospective study. Patients with nonexudative AMD. A retrospective review was performed of same-day color fundus (CF), fundus autofluorescence (FAF), near-infrared (NIR), and en face swept-source (SS) OCT images to identify eyes with nonexudative AMD and calcified drusen. The appearance and progression of these lesions were compared using the different imaging methods. Comparison between the presence of calcified drusen observed on CF images with the detection of these lesions on FAF, NIR, and en face SS OCT images. Two hundred twenty eyes from 139 patients with nonexudative AMD were studied, with 42.7% of eyes containing calcified drusen either at baseline or during follow-up visits. On the en face SS OCT images, calcified drusen appeared as dark focal lesions referred to as choroidal hypotransmission defects (hypoTDs) that were detected in the choroid using a sub–retinal pigment epithelium (RPE) slab. The corresponding B-scans showed drusen with heterogenous internal reflectivity, hyporeflective cores, and hyperreflective caps. In most calcified drusen, choroidal hypertransmission defects (hyperTDs) were observed to develop over time around the periphery of the hypoTDs, giving them the appearance of a donut lesion on the en face SS OCT images. These donut lesions were associated with significant attenuation of the overlying retina, and the corresponding FAF images showed hypoautofluorescence at the location of these lesions. The donut lesions fulfilled the requirement for a persistent hyperTD, which is synonymous with complete RPE and outer retinal atrophy (cRORA). Six eyes displayed regression of the calcified drusen without cRORA developing. B-scans at the location of these regressed calcified drusen showed deposits along the RPE, with outer retinal thinning in the regions where the calcified lesions previously existed. En face OCT imaging is a useful method for the detection and monitoring of calcified drusen and can be used to document the evolution of these drusen as they form donut lesions or foci of cRORA.

Multimodal Imaging, OCT B-Scan Localization, and En Face OCT Detection of Macular Hyperpigmentation in Eyes with Intermediate Age-Related Macular Degeneration

Abstract: PurposeMultimodal imaging was used to identify and characterize the cause of hyperpigmentation seen on color fundus images (CFIs) of eyes with intermediate age-related macular degeneration (iAMD).DesignRetrospective review of a prospective study.ParticipantsPatients with iAMD.MethodsColor fundus images with macular hyperpigmentation were compared with same-day images obtained using fundus autofluorescence (FAF), near infrared reflectance (NIR), and swept-source (SS) OCT imaging. Two SS OCT en face slabs were generated: a retinal slab to identify hyperreflective foci within the retina and a slab from beneath the retinal pigment epithelium (RPE; the sub-RPE slab) that was used to detect regions that cause decreased light transmission into the choroid, also known as hypotransmission defects. All images were registered to allow for qualitative comparisons by 2 independent graders.Main Outcome MeasuresComparison between foci of macular hyperpigmentation seen on CFIs with the detection of these regions on FAF, NIR, and SS OCT en face images.ResultsCompared with CFIs, FAF imaging seemed to be the least sensitive method for the detection of hyperpigmentation, whereas NIR and SS OCT imaging reliably detected these hyperpigmented areas. Although NIR imaging detected most of the hyperpigmentation seen in CFIs, SS OCT imaging detected all the areas of hyperpigmentation and anatomically localized these areas by using both en face and B-scan images. En face OCT slabs of the retina and sub-RPE region were registered to the CFIs, and areas of hyperpigmentation were shown to correspond to hyperreflective foci in the retina and regions of thickened RPE seen on OCT B-scans. Although both hyperpigmentation and early atrophic lesions appeared bright on NIR imaging, en face SS OCT imaging was able to distinguish these lesions because hyperpigmentary changes appeared dark and early atrophic lesions appeared bright on the sub-RPE slab.ConclusionsEn face OCT imaging in conjunction with OCT B-scans were able to identify and localize the hyperpigmentation seen in CFIs reliably. This hyperpigmentation was not only associated with intraretinal hyperreflective foci, but also corresponded to areas with a thickened RPE. Multimodal imaging was used to identify and characterize the cause of hyperpigmentation seen on color fundus images (CFIs) of eyes with intermediate age-related macular degeneration (iAMD). Retrospective review of a prospective study. Patients with iAMD. Color fundus images with macular hyperpigmentation were compared with same-day images obtained using fundus autofluorescence (FAF), near infrared reflectance (NIR), and swept-source (SS) OCT imaging. Two SS OCT en face slabs were generated: a retinal slab to identify hyperreflective foci within the retina and a slab from beneath the retinal pigment epithelium (RPE; the sub-RPE slab) that was used to detect regions that cause decreased light transmission into the choroid, also known as hypotransmission defects. All images were registered to allow for qualitative comparisons by 2 independent graders. Comparison between foci of macular hyperpigmentation seen on CFIs with the detection of these regions on FAF, NIR, and SS OCT en face images. Compared with CFIs, FAF imaging seemed to be the least sensitive method for the detection of hyperpigmentation, whereas NIR and SS OCT imaging reliably detected these hyperpigmented areas. Although NIR imaging detected most of the hyperpigmentation seen in CFIs, SS OCT imaging detected all the areas of hyperpigmentation and anatomically localized these areas by using both en face and B-scan images. En face OCT slabs of the retina and sub-RPE region were registered to the CFIs, and areas of hyperpigmentation were shown to correspond to hyperreflective foci in the retina and regions of thickened RPE seen on OCT B-scans. Although both hyperpigmentation and early atrophic lesions appeared bright on NIR imaging, en face SS OCT imaging was able to distinguish these lesions because hyperpigmentary changes appeared dark and early atrophic lesions appeared bright on the sub-RPE slab. En face OCT imaging in conjunction with OCT B-scans were able to identify and localize the hyperpigmentation seen in CFIs reliably. This hyperpigmentation was not only associated with intraretinal hyperreflective foci, but also corresponded to areas with a thickened RPE.

Depth-resolved visualization and automated quantification of hyperreflective foci on OCT scans using optical attenuation coefficients.

Abstract: An automated depth-resolved algorithm using optical attenuation coefficients (OACs) was developed to visualize, localize, and quantify hyperreflective foci (HRF) seen on OCT imaging that are associated with macular hyperpigmentation and represent an increased risk of disease progression in age related macular degeneration. To achieve this, we first transformed the OCT scans to linear representation, which were then contrasted by OACs. HRF were visualized and localized within the entire scan by differentiating HRF within the retina from HRF along the retinal pigment epithelium (RPE). The total pigment burden was quantified using the en face sum projection of an OAC slab between the inner limiting membrane (ILM) to Bruch's membrane (BM). The manual total pigment burden measurements were also obtained by combining manual outlines of HRF in the B-scans with the total area of hypotransmission defects outlined on sub-RPE slabs, which was used as the reference to compare with those obtained from the automated algorithm. 6×6 mm swept-source OCT scans were collected from a total of 49 eyes from 42 patients with macular HRF. We demonstrate that the algorithm was able to automatically distinguish between HRF within the retina and HRF along the RPE. In 24 test eyes, the total pigment burden measurements by the automated algorithm were compared with measurements obtained from manual segmentations. A significant correlation was found between the total pigment area measurements from the automated and manual segmentations (P < 0.001). The proposed automated algorithm based on OACs should be useful in studying eye diseases involving HRF.

Local Geographic Atrophy Growth Rates Not Influenced by Close Proximity to Non-Exudative Type 1 Macular Neovascularization

Abstract: Purpose The local growth rates of geographic atrophy (GA) adjacent to non-exudative type 1 macular neovascularization (MNV) were investigated to determine if MNV influenced GA growth. Methods Eyes with GA and non-exudative type 1 MNV were followed for at least 1 year. Both GA and the MNV were imaged and measured using swept-source optical coherence tomography angiography (SS-OCTA) scans. Pearson correlations were computed between local growth rates of GA, which were estimated using a biophysical GA growth model, and local distances-to-MNV. Corresponding P values for the null hypothesis of no Pearson correlation were computed using a Monte Carlo approach that adjusts for spatial autocorrelations. Results Nine eyes were included in this study. There were positive correlations (Pearson's r > 0) between distance-to-MNV and local GA growth in eight (89%) of the eyes; however, in all but one eye (11%), correlations were relatively weak and statistically nonsignificant after Bonferroni correction (corrected P > 0.05). Conclusions SS-OCTA imaging combined with GA growth modeling and spatial statistical analysis enabled quantitative assessment of correlations between local GA growth rates and local distances-to-MNV. Our results are not consistent with non-exudative type 1 MNV having a strong inhibitory effect on local GA growth rates.

Impact of Cataract Surgery on Low Luminance Visual Acuity Deficit Measurements

Abstract: The impact of cataract surgery on low luminance visual acuity deficit (LLVAD) measurements was investigated by measuring the LLVAD before and after cataract surgery.Prospective, longitudinal study.Patients undergoing cataract surgery.Photopic luminance (PL)-best-corrected visual acuity (BCVA) and low luminance (LL)-BCVA were obtained using the ETDRS chart. Low luminance visual acuity deficit scores were calculated by subtracting the LL-BCVA letter score from the PL-BCVA letter score. To demonstrate the reproducibility of these visual acuity measurements, we used data from drusen-only eyes previously published in the Complement Inhibition with Eculizumab for the Treatment of Nonexudative Age-Related Macular Degeneration (COMPLETE) study. The PL-BCVA, LL-BCVA, and LLVAD measurements obtained at an interval of 3 months in this cohort were used for comparison. In the current study, the impact of cataract surgery on LLVAD measurements was analyzed by comparing the PL-BCVA, LL-BCVA, and LLVAD measurements before and after cataract surgery.The reproducibility of the visual acuity measurements and the changes in LLVAD measurement after cataract surgery.In the COMPLETE study, no clinically significant differences were found in the PL-BCVA, LL-BCVA, or LLVAD measurements between baseline and the 3-month follow-up visits with a change of -1.1 letters, -1.3 letters, and 0.1 letters, respectively (P = 0.02, P = 0.11, and P = 0.88, respectively). In the current study, significant increases were found in the PL-BCVA and LL-BCVA measurements, with a change of 7.3 letters and 10.2 letters after cataract surgery (P < 0.001 for both), and a statistically significant decrease in LLVAD measurements was found, with a change of -3.0 letters after cataract surgery (P = 0.002).Because of the variable effect of cataracts on LL-BCVA measurements and the significant change in LLVAD measurements after cataract surgery, investigators should be aware that cataract surgery during a trial will have an unpredictable impact on LLVAD measurements, and pseudophakic and phakic patients should be analyzed separately.

Swept-source optical coherence tomography detection of bruch membrane and choriocapillaris abnormalities in sorsby macular dystrophy

Abstract: Swept-source optical coherence tomography angiography imaging of undiagnosed relatives in a family with Sorsby macular dystrophy detected reticular pseudodrusen and abnormalities in Bruch membrane thickness, choriocapillaris thickness, and choriocapillaris perfusion only in family members shown to carry the Sorsby macular dystrophy mutation. Purpose: Swept-source optical coherence tomography angiography (SS-OCTA) was used to analyze Bruch membrane (BM) and choriocapillaris (CC) abnormalities in undiagnosed family members with Sorsby macular dystrophy (SMD). Methods: In a family with SMD (TIMP3 Tyr191Cys), SS-OCTA imaging was performed using the 6 × 6 mm scan patter and previously validated algorithms to detect abnormalities in BM and the CC, as well as the presence of reticular pseudodrusen and macular neovascularization. Genetic analyses were performed for TIMP3 mutations. Results: Of eight family members, two were previously diagnosed with SMD and six were asymptomatic. SS-OCTA imaging of the 33-year-old proband revealed type 1 macular neovascularization in the left eye and bilateral reticular pseudodrusen, thickening of BM, CC thinning, and increases in CC flow deficits. A TIMP3 mutation was confirmed. His niece, despite having no clinical evidence of SMD, showed BM thickening and CC thinning on SS-OCTA. A TIMP3 mutation was confirmed. The proband's younger nephew and niece also carried the TIMP3 mutation without clinical evidence of SMD. Two additional members had normal examinations, unremarkable SS-OCTA findings, and no TIMP3 mutation. Conclusion: Swept-source optical coherence tomography angiography imaging can detect BM and CC abnormalities in vivo in subjects unaware of their TIMP3 status in a family with SMD.

Comparing Accuracies of Length-Type Geographic Atrophy Growth Rate Metrics Using Atrophy-Front Growth Modeling

Abstract: To compare the accuracies of the previously proposed square-root-transformed and perimeter-adjusted metrics for estimating length-type geographic atrophy (GA) growth rates.Cross-sectional and simulation-based study.Thirty-eight eyes with GA from 27 patients.We used a previously developed atrophy-front growth model to provide analytical and numerical evaluations of the square-root-transformed and perimeter-adjusted growth rate metrics on simulated and semisimulated GA growth data.Comparison of the accuracies of the square-root-transformed and perimeter-adjusted metrics on simulated and semisimulated GA growth data.Analytical and numerical evaluations showed that the accuracy of the perimeter-adjusted metric is affected minimally by baseline lesion area, focality, and circularity over a wide range of GA growth rates. Average absolute errors of the perimeter-adjusted metric were approximately 20 times lower than those of the square-root-transformed metrics, per evaluation on a semisimulated dataset with growth rate characteristics matching clinically observed data.Length-type growth rates have an intuitive, biophysical interpretation that is independent of lesion geometry, which supports their use in clinical trials of GA therapeutics. Taken in the context of prior studies, our analyses suggest that length-type GA growth rates should be measured using the perimeter-adjusted metric, rather than square-root-transformed metrics.

Change in choriocapillaris flow deficits within tears of the retinal pigment epithelium imaged with swept-source optical coherence tomography angiography

Abstract: Swept-source optical coherence tomography angiography imaging of three patients before and after the onset of retinal pigment epithelium tears showed that choriocapillaris flow deficit measurements remained stable within the bed of the retinal pigment epithelium tears for at least 16 months after their onset. Purpose: Choriocapillaris (CC) flow deficits (FDs) were measured in the areas exposed by tears of the retinal pigment epithelium (RPE) before and after their onset to determine their change over time. Methods: Patients enrolled in a prospective, swept-source optical coherence tomography angiography (SS-OCTA) study were retrospectively reviewed for RPE tears, and scans were evaluated before and after RPE tear formation. Choriocapillaris flow deficits were measured within the bed of the tear and within a symmetric control region. Results: Three patients with RPE tears were imaged before tear formation and for at least 16 months afterward. When the baseline and first posttear visit were compared, CC FDs decreased by 1.0% in the tear region and 1.7% in the control region (P = 0.84). When the 16-month follow-up visits were compared with the first post-RPE tear visits, CC FDs decreased by 1.9% in tear regions and increased by 1.3% in control regions (P = 0.37). Conclusion: No significant changes in CC FDs were observed before and after RPE tear formation and for 16 months afterward, suggesting that CC FDs can be reliably detected in the presence of an intact RPE and the absence of the RPE did not affect CC perfusion for at least 16 months.

Detection of Nonexudative Macular Neovascularization on Structural OCT Images Using Vision Transformers

Abstract: A deep learning model was developed to detect nonexudative macular neovascularization (neMNV) using OCT B-scans.Retrospective review of a prospective, observational study.Normal control eyes and patients with age-related macular degeneration (AMD) with and without neMNV.Swept-source OCT angiography (SS-OCTA) imaging (PLEX Elite 9000, Carl Zeiss Meditec, Inc) was performed using the 6 × 6-mm scan pattern. Individual B-scans were annotated to distinguish between drusen and the double-layer sign (DLS) associated with the neMNV. The machine learning model was tested on a dataset graded by humans, and model performance was compared with the human graders.Intersection over Union (IoU) score was measured to evaluate segmentation network performance. Area under the receiver operating characteristic curve values, sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were measured to assess the performance of the final classification performance. Chance-corrected agreement between the algorithm and the human grader determinations was measured with Cohen's kappa.A total of 251 eyes from 210 patients, including 182 eyes with DLS and 115 eyes with drusen, were used for model training. Of 125 500 B-scans, 6879 B-scans were manually annotated. A vision transformer segmentation model was built to extract DLS and drusen from B-scans. The extracted prediction masks from all B-scans in a volume were projected to an en face image, and an eye-level projection map was obtained for each eye. A binary classification algorithm was established to identify eyes with neMNV from the projection map. The algorithm achieved 82%, 90%, 79%, and 91% sensitivity, specificity, PPV, and NPV, respectively, on a separate test set of 100 eyes that were evaluated by human graders in a previous study. The area under the curve value was calculated as 0.91 (95% confidence interval, 0.85-0.98). The results of the algorithm showed excellent agreement with the senior human grader (kappa = 0.83, P < 0.001) and moderate agreement with the junior grader consensus (kappa = 0.54, P < 0.001).Our network (code is available at https://github.com/uw-biomedical-ml/double_layer_vit) was able to detect the presence of neMNV from structural B-scans alone by applying a purely transformer-based model.

Impact of Reticular Pseudodrusen on Choriocapillaris Flow Deficits and Choroidal Structure on Optical Coherence Tomography Angiography

Abstract: Purpose To examine the impact of reticular pseudodrusen (RPD) on choriocapillaris blood flow and choroidal structure in individuals with intermediate age-related macular degeneration (AMD). Methods Individuals with bilateral large drusen underwent optical coherence tomography (OCT), color fundus photography, near-infrared reflectance, and fundus autofluorescence imaging to determine the presence of RPD. These participants also underwent swept-source OCT angiography (SS-OCTA) imaging to determine (1) choriocapillaris flow deficit (FD) parameters, including the percentage, mean size, and number of FDs present; and (2) choroidal structural parameters, including mean choroidal thickness and choroidal vascularity index. Differences in these parameters between eyes with and without coexistent RPD were examined with and without adjustment for potential key confounders such as drusen volume from the SS-OCTA scans and age. Results This study included 102 eyes from 51 individuals with bilateral large drusen, and the analyses showed that there were no significant differences in the choriocapillaris FD parameters (P ≥ 0.062 for all) and choroidal structural parameters (P ≥ 0.059 for all), with or without adjustment for potential confounders in this cohort. However, the percentage of FDs and the mean FD size were both significantly greater with increasing drusen volume (P ≤ 0.038 for both). Conclusions The coexistence of RPD in eyes of individuals with intermediate AMD was not associated with significant impairments in choriocapillaris blood flow and choroidal vascular structural changes, with or without adjustment for key confounders. These findings suggest that macular changes in these vascular parameters may not be associated with the presence of RPD.

Author Response: Local Geographic Atrophy Growth Rates Not Influenced by Close Proximity to Non-Exudative Type 1 Macular Neovascularization

Abstract: We thank Pfau et al. for their thoughtful letter regarding our recent article.1 Their letter raises several interesting and important points, which we address below. Pfau et al. are correct in writing that we computed P values for each eye separately and that we did not condition our analyses on geographic atrophy (GA) growth rates from natural history studies or fellow eyes. However, the hypothesis tested in our paper pertains to local (i.e. spatially resolved) relationships, and therefore is inherently intraeye. In particular, our hypothesis involves comparing growth rates along different segments of the same GA lesion, making (global) growth rates of lesions in other eyes not relevant to the hypothesis under consideration in our paper. Note that the “spatially specific hypothesis,” as defined in their letter, is also intra-eye. The corresponding inter-eye (population level) hypothesis is that global (i.e. spatially unresolved) GA growth rates are reduced by the presence of non-exudative type 1 macular neovascularization (MNV). Although the global hypothesis is certainly of interest, it was not a focus of our study. We broadly agree with Pfau et al. that there is merit to distinguishing the spatially specific hypothesis from the “halo hypothesis.” However, we consider these two hypotheses to represent a difference in degree rather than in kind, with the former a limiting case of the latter—namely, if the “halo” is made very small, one naturally arrives at the spatially specific hypothesis. Thus, the relevant question pertains to the most appropriate size of the halo. Although we remain uncommitted on this question, we do briefly mention some possibilities in the Discussion portion of our paper using the term “neighborhood-of-influence” rather than halo, and we partially address it by considering both an all-distances halo and a 1 mm halo. Indeed, we believe that our analysis is well suited to detecting effects across the range of plausible halo sizes—including the spatially specific limit. For example, if the spatially specific hypothesis were true, we would expect to see a sharp jump in the scatter plots of the local growth GA growth rates versus distances-toMNV. However, such a trend was not present (Figures 3–5).1 We have some disagreement with Pfau et al. regarding their interpretation of Figures 3–5 of our paper. Specifically, Pfau et al. wrote that these figures “...reveal a slower median RPE atrophy progression in the subregion co-localizing with MNV (0 to 0.1 mm subregion) compared to the overall median elsewhere (patients 1, 4, 5, 7, 8, and 9 [i.e. 6 of 9 patients])...”. However, in case 8, the configuration of the MNV and GA is such that there are no GA margin points— at all—in the 0 to 0.1 mm range, and so case 8 can neither support nor refute the spatially specific hypothesis. Furthermore, in case 5, the median growth rate in the 0 to 0.1 mm range is higher than that in the adjacent 0.1 to 0.2 mm and 0.2 to 0.3 mm ranges. Because points in the neighboring ranges would be the most natural “controls” for the spatially specific hypothesis, but not, incidentally for the halo hypothesis, case 5 also does not support the spatially specific hypothesis. This reduces the tally to four of nine patients. Finally, there is the question of statistical significance. Because GA growth rates have a substantial spatial autocorrelation—that is, nearby margin segments tend to have similar growth rates—it would not be unlikely that by sheer chance the margin segments in the 0.1 to 0.2 mm range enlarge slower (or faster) than margin segments farther from the MNV, in some cases. We believe that accounting for this autocorrelation is important for reducing type I error rates. Finally, we want to emphasize our belief that atrophy embedded within MNV, most likely arising from a preexisting MNV, is of a different etiology and character than that of GA that independently developed,2,3 and, consequently, that the subjects of our study may not be directly comparable to those of the study by Pfau et al.4 In conclusion, we thank Pfau and colleagues for their interest and engagement in this exciting topic and believe that they raise important points, particularly regarding the distances over which MNV lesions may influence GA growth rates. Although not addressed by our study, we also believe that the effects of MNV on global GA growth rates is an important topic for future investigations. Finally, we echo their letter in emphasizing the need for larger prospective studies.

Regression of Bilateral Peripapillary Choroidal Neovascularization Associated with Idiopathic Intracranial Hypertension after Systemic Acetazolamide Treatment

Abstract: A rare occurrence of bilateral peripapillary choroidal neovascularization (CNV) in an 18-year-old idiopathic intracranial hypertension (IIH) patient regressed with systemic acetazolamide treatment alone. Multimodal imaging was done, including OCT angiography (OCTA), which showed CNV. No injections were given even though she had macular fluid in her left eye. Nonetheless, the subretinal fluid resolved, and visual acuity improved. This report shows that CNV secondary to IIH can be managed with systemic therapy alone. Moreover, we showed for the first time the ability to diagnose IIH-associated CNV using OCTA.