Papers by Prem Subramanian
Scientific Reports, Oct 12, 2022
This work aims at determining the ability of a deep learning (DL) algorithm to measure retinal ne... more This work aims at determining the ability of a deep learning (DL) algorithm to measure retinal nerve fiber layer (RNFL) thickness from optical coherence tomography (OCT) scans in anterior ischemic optic neuropathy (NAION) and demyelinating optic neuritis (ON). The training/validation dataset included 750 RNFL OCT B-scans. Performance of our algorithm was evaluated on 194 OCT B-scans from 70 healthy eyes, 82 scans from 28 NAION eyes, and 84 scans of 29 ON eyes. Results were compared to manual segmentation as a ground-truth and to RNFL calculations from the built-in instrument software. The Dice coefficient for the test images was 0.87. The mean average RNFL thickness using our U-Net was not different from the manually segmented best estimate and OCT machine data in control and ON eyes. In NAION eyes, while the mean average RNFL thickness using our U-Net algorithm was not different from the manual segmented value, the OCT machine data were different from the manual segmented values. In NAION eyes, the MAE of the average RNFL thickness was 1.18 ± 0.69 μm and 6.65 ± 5.37 μm in the U-Net algorithm segmentation and the conventional OCT machine data, respectively (P = 0.0001). Optical coherence tomography (OCT) has been applied to measure peripapillary retinal nerve fiber layer (RNFL) thickness at a micrometer scale in several optic neuropathies such as non-arteritic anterior ischemic optic neuropathy (NAION) and demyelinating optic neuritis (ON) 1-3 . In the early stages of NAION and papillitis, OCT of the RNFL may show thickening that decreases in the subacute phase. An accurate measurement of the thickness is important as RNFL thickness may be useful for detection of disease progression or improvement 2,3 . Commercial OCT machines use automated retinal layer segmentation algorithms to detect the difference in signal intensity between adjacent retinal layers to calculate RNFL thickness. However, the scans can be affected by movement, media opacity, algorithm failure or poor signal to noise ratios and misidentification of the anterior and posterior boundaries of the RNFL and incomplete segmentation are artifacts that are consistently described in glaucoma eyes . In some studies, the artifact rates of 46.3% and 61.7% for OCT B scans in glaucoma eyes were reported 4,7 . Such errors may cause false measurements of the thicknesses of the different layers and structures. Of note, the baseline errors persist into the subsequent scans, and errors are propagated longitudinally 8 . Therefore, manual refinement of OCT retinal layer segmentation when assessing RNFL thickness by an operator is recommended, but this process is laborious and extremely time consuming. While previous studies have not determined the segmentation issues and artifacts in other optic neuropathies such as NAION and ON, it has been reported in a case report that segmentation errors can lead to clinical misdiagnosis of neuro-ophthalmic diseases if they go unrecognized 9 . Deep learning (DL) is a type of artificial intelligence that uses multilayer neural networks, and its algorithms outperform ophthalmologists in disease detection 10 . Furthermore, DL algorithms have been trained to detect errors in automated RNFL segmentation of OCT scans in glaucoma, identifying the probability of a segmentation artifact as well as highlighting the location of these errors using a heat-map with an accuracy of 92.4% 11 . However, studies are lacking about the use of DL for RNFL segmentation in NAION and ON eyes.
Journal of Neuro-Ophthalmology
Background: To evaluate the classification performance of machine learning based on the 4 vessel ... more Background: To evaluate the classification performance of machine learning based on the 4 vessel density features of peripapillary optical coherence tomography angiography (OCT-A) for classifying healthy, nonarteritic anterior ischemic optic neuropathy (NAION), and optic neuritis (ON) eyes. Methods: Forty-five eyes of 45 NAION patients, 32 eyes of 32 ON patients, and 76 eyes of 76 healthy individuals with optic nerve head OCT-A were included. Four vessel density features of OCT-A images were developed using a threshold-based segmentation method and were integrated in 3 models of machine learning classifiers. Classification performances of support vector machine (SVM), random forest, and Gaussian Naive Bayes (GNB) models were evaluated with the area under the receiver-operating-characteristic curve (AUC) and accuracy. Results: We divided 121 images into a 70% training set and 30% test set. For ON-NAION classification, best results were achieved with 50% threshold, in which 3 classifi...
Journal of Neuro-Ophthalmology
Clinical & Experimental Ophthalmology
Frontiers in ophthalmology, Apr 20, 2023
A significant role of the neuro-ophthalmologist is to counsel patients on appropriate management ... more A significant role of the neuro-ophthalmologist is to counsel patients on appropriate management and anticipated visual prognosis for conditions affecting the afferent and efferent visual systems, including those requiring neurosurgical treatment. However, the literature regarding anticipated neuroophthalmologic prognosis after neurosurgical intervention for cerebral aneurysms, sellar lesions, optic pathway tumors, and elevated intracranial pressure is limited with many key questions unanswered. For example, if a cerebral aneurysm is equally amenable to clipping or endovascular coiling, is there a preferred approach in terms of visual prognosis based on aneurysm location? Is dural venous sinus stenting (VSS) for idiopathic intracranial hypertension (IIH) superior, equivalent or inferior to shunting in terms of visual recovery and safety profile? Landmark studies on pituitary tumors using preoperative optical coherence tomography (OCT) imaging of the optic nerve head to predict visual recovery after surgical decompression of the optic chiasm have changed neuro-ophthalmologic practice and enabled patients to be better informed regarding expected visual outcomes. 1,2 In order to optimize an interdisciplinary team approach to patient care, further studies of visual outcomes for neuro-ophthalmologic conditions requiring neurosurgical intervention are needed.
bioRxiv (Cold Spring Harbor Laboratory), Mar 21, 2023
Due to long-standing federal restrictions on cannabis-related research, the implications of canna... more Due to long-standing federal restrictions on cannabis-related research, the implications of cannabis legalization on traffic and occupational safety are understudied. Accordingly, there is a need for objective and validated measures of acute cannabis impairment that may be applied in public safety and occupational settings. Pupillary response to light may offer an avenue for detection that outperforms typical sobriety tests and THC concentrations. We developed a video processing and analysis pipeline that extracts pupil sizes during a light stimulus test administered with goggles utilizing infrared videography. The analysis compared pupil size trajectories in response to a light for those with occasional, daily, and no cannabis use before and after smoking. Pupils were segmented using a combination of image pre-processing techniques and segmentation algorithms which were validated using manually segmented data and found to achieve 99% precision and 94% F-score. Features extracted from the pupil size trajectories captured pupil constriction and rebound dilation and were analyzed using generalized estimating equations. We find that acute cannabis use results in less pupil constriction and slower pupil rebound dilation in the light stimulus test.
American Journal of Ophthalmology
Frontiers in Neurology
Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis op... more Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatment timing or antibody serostatus. The Acute Optic Neuritis Network (ACON) presents a global, prospective, observational study protocol primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. Patients presenting within 30 days of the inaugural ON will be enrolled. For the primary analysis, patients will subsequently be assigned into the MS-ON group, the aquapotin-4-IgG positive ON (AQP4-IgG+ON) group or the MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from the onset of visual loss to high-dose corticosteroids (days...
Ophthalmic Plastic & Reconstructive Surgery
Purpose: Severe burn patients require high-volume fluid resuscitation, which increases risk for o... more Purpose: Severe burn patients require high-volume fluid resuscitation, which increases risk for orbital compartment syndrome (OCS). We aimed to understand surgeons’ practice patterns and to examine risk factors for OCS, timing of lateral canthotomy and cantholysis (LCC), and complications of intervention. Methods: A survey of American Society of Ophthalmic Plastic and Reconstructive Surgery and North American Society of Academic Orbital Surgeons’ practice patterns in burn patients was undertaken. In addition, a retrospective analysis was conducted of 107 patients with burns greater than 20% total body surface area at 1 institution from January 1, 2009, to June 1, 2018. Patients with Stevens–Johnson Syndrome or Toxic Epidermal Necrolysis, frostbite, or no ophthalmologic consultation were excluded. Risk factors for OCS, timing of LCC, and complications of the intervention were examined. Results: In the survey, 37 of 54 respondents had treated burn patients, of which 29 followed no pro...
Acta Ophthalmologica
Purpose: To evaluate the efficacy and safety of a bilateral injection of lenadogene nolparvovec i... more Purpose: To evaluate the efficacy and safety of a bilateral injection of lenadogene nolparvovec in patients with Leber Hereditary Optic Neuropathy (LHON) carrying the m.11778G > A mutation.Methods: REFLECT is a randomized, placebo‐controlled, phase 3 study that included 98 patients with vision loss ≤1 year at enrolment. Patients received a single intravitreal injection of lenadogene nolparvovec (9E10 viral genomes per eye) in their first‐affected eye. The second‐affected eye was randomized to a second injection of gene therapy or placebo.Results: A total of 48 patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in best‐corrected visual acuity (BCVA) of the second‐affected eyes was not statistically different between the two arms (primary endpoint). Two years after injection, a statistically significant improvement in BCVA was reported from baseline in treated eyes. Mean BCVA showed an absolute difference between the arms of +6 ETDRS lette...
Journal of Neuro-Ophthalmology
Neurology: Clinical Practice
Optometric visual rehabilitation therapy has been used for a variety of visual disorders. Descrip... more Optometric visual rehabilitation therapy has been used for a variety of visual disorders. Descriptively named entities such as posttrauma visual syndrome, visual midline shift syndrome, and vertical heterophoria syndrome are frequently diagnosed by neuro-optometrists and/or behavioral optometrists in patients after stroke or head injury or in the setting of dizziness and/or headache. The scientific underpinnings of these diagnoses and treatments are weak, and published clinical studies comprise case reports and case series without comparison to control populations. Neuro-ophthalmologists are frequently questioned by patients about the utility of such treatment strategies. Many ophthalmologists and neurologists also are involved in the care of patients who carry these diagnoses and undergo these visual therapies. Involved physicians may benefit from guidance about the rationale, evidence, and level of evidence for the efficacy of these therapeutic approaches.
JAMA Ophthalmology
IMPORTANCE Thyroid eye disease can be a debilitating autoimmune disorder characterized by progres... more IMPORTANCE Thyroid eye disease can be a debilitating autoimmune disorder characterized by progressive proptosis or diplopia. Teprotumumab has been compared with placebo in randomized clinical trials, but not with intravenous methylprednisolone (IVMP), which sometimes is used in clinical practice for this condition. OBJECTIVE To conduct a matching-adjusted indirect comparison of teprotumumab vs IVMP vs placebo. DATA SOURCES Deidentified patient-level data from teprotumumab trials and aggregate-level data from literature on the most recommended regimen of IVMP. STUDY SELECTION PubMed and Embase were searched for randomized/observational studies using key terms and controlled vocabulary. Full texts of eligible articles were reviewed and cataloged. Conducted by 1 reviewer (R.A.Q.) and 1 verifier (R.B.), including study characteristics, eligibility criteria, baseline characteristics, and outcomes. Changes in proptosis by millimeter and diplopia response (percentage with Ն1 grade reduction) from baseline to week 12 in patients receiving IVMP and placebo, and to week 24 in patients receiving teprotumumab. The search identified 1019 records, and 6 through manual searches, alerts, and secondary references. After excluding duplicates and screening full-text records, 12 IVMP studies were included in the matching-adjusted indirect comparison (11 for proptosis change [n = 419], 4 for diplopia response [n = 125], and 2 teprotumumab [n = 79] and placebo [n = 83] comparator studies). Treatment with IVMP resulted in a proptosis difference of -0.16 mm (95% CI, -1.55 to 1.22 mm) from baseline to week 12 vs placebo. The proptosis treatment difference between IVMP and teprotumumab of -2.31 mm (95% CI, -3.45 to -1.17 mm) favored teprotumumab. Treatment with IVMP (odds ratio, 2.69; 95% CI, 0.94-7.70) was not favored over placebo in odds of diplopia response; however, teprotumumab was favored over IVMP (odds ratio, 2.32; 95% CI, 1.07-5.03). This meta-analysis suggests that use of IVMP is associated with a small, typically not clinically relevant, change from baseline in proptosis vs placebo, with modest changes in diplopia. While this nonrandomized comparison suggests that use of teprotumumab, compared with IVMP, is associated with greater improvements in proptosis and may be twice as likely to have a 1 grade or higher reduction in diplopia, randomized trials comparing these 2 treatments would be warranted to determine if 1 treatment is superior to the other to a clinically relevant degree.
F1000 - Post-publication peer review of the biomedical literature, 2020
Multiple Sclerosis and Related Disorders, 2020
BACKGROUND Ganglion cell inner plexiform (GCIP) layer thinning following acute optic neuritis (ON... more BACKGROUND Ganglion cell inner plexiform (GCIP) layer thinning following acute optic neuritis (ON) is well-known. However, the onset of changes in the outer retinal layers needs further study. In this study, we determine longitudinal changes in retinal layer thickness in ON. METHODS Thirty ON patients underwent optical coherence tomography (OCT) and visual function testing at baseline, one month, and 6 months. RESULTS Mean GCIPL thickness decreased at one month relative to baseline from 63.6 ± 7.5 μm to 57.3 ± 6.8 µm in 3 mm ring (P < 0.001). There were no significant changes in GCIPL thickness between one and 6 months (P = 0.42). Outer nuclear layer (ONL) thickness in the 6 mm macular area increased from 58.9 ± 5.8 µm to 63.2 ± 6.8 μm at one month (P < 0.001) and then decreased at six month (58.8 ± 5.8 µm) relative to one month, reaching the baseline thickness. While GCIPL thinning at 1 month correlated with baseline visual acuity, change in the central ONL thickness from baseline to month 1 predicted visual outcome at month 6 (r = 0.6, P = 0.001). CONCLUSIONS Following ON, transient changes occur in the photoreceptor nuclei layer and then revert to baseline. This finding could predict 6 month visual acuity after ON.
Asia-Pacific Journal of Ophthalmology, 2019
Journal of American Association for Pediatric Ophthalmology and Strabismus, 2018
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Papers by Prem Subramanian