Thomas H Dohlman, Matthew McSoley, Francisco Amparo, Tatiana Carreno-Galeano, Mengyu Wang, Mohammad Dastjerdi, Rohan Bir Singh, Giulia Coco, Antonio Di Zazzo, and Hasanain Shikari. 2022. “Bevacizumab in High-Risk Corneal Transplantation: a Pilot Multi-Center Prospective Randomized Control Trial.” Ophthalmology. Publisher's VersionAbstract

Purpose: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin®) treatment in patients undergoing vascularized high-risk corneal transplantation.

Design: Pilot prospective, randomized, double-blind, placebo-controlled clinical trial conducted at five clinical centers in the United States, India and Brazil.

Participants: Patients over the age of 18 undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in one or more quadrants ≥ 2mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft.

Intervention: Patients were randomized to receive either subconjunctival bevacizumab (2.5mg/0.1ml) or placebo at the time of surgery, followed by topical bevacizumab (10mg/ml) or topical placebo, administered four times per day for four weeks.

Main outcome measure: 52-week endothelial immune rejection rate.

Results: Ninety-two patients were randomized to receive bevacizumab (n=48) or control (n=44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (p=0.20). Post-hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (p=0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% CI: [0.03-0.65], p=0.01) in a post-hoc Cox regression analysis.

Conclusions: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at one year in in the bevacizumab treatment group as compared to the control group. This study may have been under-powered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.

Keywords: angiogenesis; corneal transplantation; neovascularization; penetrating keratoplasty; vascular endothelial growth factor.

Parul Ichhpujani, Sahil Thakur, Tanu Singh, Rohan Bir Singh, and Suresh Kumar. 2022. “Effect of laser peripheral iridotomy on contrast sensitivity using Spaeth/Richman Contrast Sensitivity test.” Therapeutic Advances in Ophthalmology, 14, Pp. 25158414221078142. Publisher's VersionAbstract

Background: Laser peripheral iridotomy (LPI) is the current standard of care for primary angle-closure glaucoma. The existing literature lacks evidence regarding the effects of LPI on contrast sensitivity (CS) after the procedure.

Objective: This study evaluates central and peripheral CS in patients undergoing LPI using the computer-based, Spaeth/Richman Contrast Sensitivity (SPARCS) test.

Methods: We performed a pilot, prospective, interventional cohort study including 30 patients of primary angle-closure suspect (PACS) or primary angle closure (PAC) in both eyes. LPI was performed after a detailed history and clinical examination using standard procedure in all eyes. Intraocular pressure (IOP) and CS testing using SPARCS was performed before, 2 weeks and 3 months after LPI.

Results: Data analyses revealed female predominance (66.67%, 20/30); the mean age of enrolled patients was 49.93 ± 10.43 years, and presenting acuity was 0.02 ± 0.06 (Log of Minimum Angle of Resolution [LogMAR]). The mean vertical cup-to-disc ratio (VCDR), mean deviation (MD in dB) and pattern standard deviation (PSD in dB) were 0.34 ± 0.09, -2.36 ± 1.72 and 2.34 ± 0.81, respectively. There was a statistically significant decrease between the pre- (15.17 ± 3.83 mmHg) and 2 weeks post-LPI (11.70 ± 1.53 mmHg) IOP (p < 0.001). However, CS in the pre- (73.47 ± 9.88) and 3 months post-LPI (75.20 ± 11.98) SPARCS scores did not reveal any statistical difference. The group-wise analysis showed a similar trend between PAC and PACS patients.

Conclusion: LPI does not affect central as well as peripheral CS assessment in patients with the primary angle-closure disease.

Keywords: PAC; PACS; SPARCS; glaucoma; laser peripheral iridotomy; primary angle-closure disease.

Daniela Claessens, Parul Ichhpujani, and Rohan Bir Singh. 2022. “MacuFix® versus Amsler grid for metamorphopsia categorization for macular diseases.” International Ophthalmology, 42, 1, Pp. 229-238. Publisher's VersionAbstract

Purpose: Macular diseases often lead to metamorphopsia, which is traditionally tested using the Amsler grid. This study evaluates a novel method for assessing metamorphopsia, based on the software AMD-A Metamorphopsia Detector, application MacuFix®.

Methods: In this observational study, the usability of a new smartphone-based testing method to assess metamorphopsia was evaluated in 45 patients experiencing metamorphopsia in at least one eye using the questionnaire "System Usability Score (SUS)." Additionally, the diagnostic adherence of self-monitoring with the Amsler grid was compared to self-monitoring with the novel software MacuFix®.

Results: The average score of the SUS questionnaire in this study was 76.7 ± 15.5, corresponding to the "good" score on the grading scale. The average interval between two home administered tests was significantly shorter (6 days) when the application was used as compared to using the Amsler grid (19 days). The odds ratio of the frequency of patients using the application to the patients using the home test was 4.

Conclusion: MacuFix® application can help in effective home monitoring of macular function as high user satisfaction and increased testing frequency was observed in its use in patients with macular diseases.


Thomas H Dohlman, Rohan Bir Singh, and Reza Dana. 2021. “Advances in the Medical Management of Neurotrophic Keratitis.” Semin Ophthalmol, 36, 4, Pp. 335-340.Abstract
Neurotrophic Keratitis (NK) is a degenerative disorder of the cornea characterized by decreased or absent sensory corneal innervation, corneal epitheliopathy and impaired healing.The clinical presentation of NK can range from persistent epithelial defects to corneal perforation and management is often both challenging and protracted. Historically, the management of NK has consisted of non-specific strategies to facilitate corneal epithelial healing such as lubrication, bandage contact lenses and tarsorrhaphy. Recent advances in the development of therapeutics for NK have provided new and efficacious targeted strategies for its management.In this article, we review recombinant human nerve growth factor (Cenegermin), currently approved for clinical use in the United States and Europe, as well as other promising therapeutic options that are in pre-clinical development such as thymosine β4, connexin43 inhibitors, and artificial extracellular matrix components.
Maryam Tahvildari, Rohan Bir Singh, and Hajirah N Saeed. 2021. “Application of Artificial Intelligence in the Diagnosis and Management of Corneal Diseases.” Semin Ophthalmol, Pp. 1-8.Abstract
Diagnosis and treatment planning in ophthalmology heavily depend on clinical examination and advanced imaging modalities, which can be time-consuming and carry the risk of human error. Artificial intelligence (AI) and deep learning (DL) are being used in different fields of ophthalmology and in particular, when running diagnostics and predicting outcomes of anterior segment surgeries. This review will evaluate the recent developments in AI for diagnostics, surgical interventions, and prognosis of corneal diseases. It also provides a brief overview of the newer AI dependent modalities in corneal diseases.
Shruti Muralidharan, Parul Ichhpujani, Shibal Bhartiya, and Rohan Bir Singh. 2021. “Eye-tunes: role of music in ophthalmology and vision sciences.” Therapeutic Advances in Ophthalmology, 13, Pp. 25158414211040890.
Tanu Singh, Parul Ichhpujani, and Rohan Bir Singh. 2021. “First Line of Defense in COVID-19: Masks in Clinical Practice.” Asia Pac J Public Health, 33, 1, Pp. 147-149.
Yvonne Wang, Jimena Tatiana Carreno-Galeano, Rohan Bir Singh, Reza Dana, and Jia Yin. 2021. “Long-term Outcomes of Punctal Cauterization in the Management of Ocular Surface Diseases.” Cornea, 40, 2, Pp. 168-171.Abstract
PURPOSE: To evaluate the long-term outcomes of surgical occlusion of lacrimal puncta using thermal cautery in the management of ocular surface diseases. METHODS: We reviewed medical records of 80 consecutive patients from a single academic center who underwent punctal cauterization. Patient demographics, ocular history, symptoms, and signs of ocular surface diseases pre- and post-cauterization were recorded. RESULTS: A total of 80 patients (171 puncta) were included, with an average age of 59 years and a follow-up duration of 27 months. The most common ocular morbidity was ocular graft-versus-host disease (n = 36), followed by primary keratoconjunctivitis sicca (n = 15). Indications for punctal cauterization included plug loss (n = 51), difficulty in plug fitting (n = 11), plug-related complications (n = 6), recanalization of previous cauterization (n = 7), and severe ocular surface disease requiring permanent punctal closure (n = 4). After punctal cauterization, the percentage of eyes with severe (21%) and moderate (25%) dry eye decreased significantly (8% and 19% at 3 months and 6% and 17% at 12 months, P = 0.0006). Fifty-four percent of patients reported improvement in their symptoms. The rate of recanalization was 21% during the follow-up period. The use of topical corticosteroids was associated with higher recanalization rate. Associated complications were limited to temporary pain and swelling. CONCLUSIONS: Punctal cauterization is an effective modality in treating severe ocular surface diseases in patients who repeatedly lose punctal plugs, and it can be easily performed in a clinic setting without major complications. However, cauterization may need to be repeated in up to a quarter of cases because of recanalization.
Sachi Singhal, Rohan Bir Singh, and Rashmika Potdar. 2021. “Metastatic squamous cell carcinoma of the colon: a conundrum in colorectal malignancies.” BMJ Case Rep, 14, 4.Abstract
Small-cell carcinoma of the colon is an extremely rare tumour, with poorly understood pathogenesis and unestablished treatment guidelines. The first case was documented in 1919, and only about 100 cases of this condition have been reported to this date. In this case report, we present a case of sigmoid squamous cell carcinoma that eventually led to bowel perforation and was diagnosed on histopathology after emergent surgical intervention. Additionally, we also review the incidence, epidemiology, pathogenesis, immunohistological markers, neogenomics and therapeutic strategies for the same.
Rohan Bir Singh, Tanvi Khera, Victoria Ly, Chhavi Saini, Wonkyung Cho, Sukhman Shergill, Kanwar Partap Singh, and Aniruddha Agarwal. 2021. “Ocular complications of perioperative anesthesia: a review.” Graefes Arch Clin Exp Ophthalmol.Abstract
Ocular complications associated with anesthesia in ocular and non-ocular surgeries are rare adverse events which may present with clinical presentations vacillating between easily treatable corneal abrasions to more serious complication such as irreversible bilateral vision loss. In this review, we outline the different techniques of anesthetic delivery in ocular surgeries and highlight the incidence and etiologies of associated injuries. The changes in vision in non-ocular surgeries are mistaken for residual sedation or anesthetics, therefore require high clinical suspicion on part of the treating ophthalmologists, to ensure early diagnosis, adequate and swift management especially in surgeries such as cardiac, spine, head and neck, and some orthopedic procedures, that have a comparatively higher incidence of ocular complications. In this article, we review the literature for reports on the clinical incidence of different ocular complications associated with anesthesia in non-ocular surgeries and outline the current understanding of pathophysiological processes associated with these adverse events.
Rohan Bir Singh, Prakash Gupta, Akash Kartik, Naba Farooqui, Sachi Singhal, Sukhman Shergill, Kanwar Partap Singh, and Aniruddha Agarwal. 2021. “Ocular Manifestations of Neuronal Ceroid Lipofuscinoses.” Seminars in Ophthalmology 36 (7), Pp. 582-595. Taylor & Francis.
Rohan Bir Singh, Lingjia Liu, Ann Yung, Sonia Anchouche, Sharad K Mittal, Tomas Blanco, Thomas H Dohlman, Jia Yin, and Reza Dana. 2021. “Ocular redness - II: Progress in development of therapeutics for the management of conjunctival hyperemia.” Ocul Surf, 21, Pp. 66-77.Abstract
Conjunctival hyperemia is one of the most common causes for visits to primary care physicians, optometrists, ophthalmologists, and emergency rooms. Despite its high incidence, the treatment options for patients with conjunctival hyperemia are restricted to over-the-counter drugs that provide symptomatic relief due to short duration of action, tachyphylaxis and rebound redness. As our understanding of the immunopathological pathways causing conjunctival hyperemia expands, newer therapeutic targets are being discovered. These insights have also contributed to the development of animal models for mimicking the pathogenic changes in microvasculature causing hyperemia. Furthermore, this progress has catalyzed the development of novel therapeutics that provide efficacious, long-term relief from conjunctival hyperemia with minimal adverse effects.
Rohan Bir Singh, Sujata Das, James Chodosh, Namrata Sharma, Michael E Zegans, Regis P Kowalski, and Vishal Jhanji. 2021. “Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis.” Progress in retinal and eye research, Pp. 101028.
Rohan B Singh, Tomas Blanco, Sharad K Mittal, Hamid Alemi, Sunil K Chauhan, Yihe Chen, and Reza Dana. 2021. “Pigment Epithelium-Derived Factor Enhances the Suppressive Phenotype of Regulatory T Cells in a Murine Model of Dry Eye Disease.” Am J Pathol, 191, 4, Pp. 720-729.Abstract
Pigment epithelium-derived factor (PEDF) is a widely expressed 50-kDa glycoprotein belonging to the serine protease inhibitor family, with well-established anti-inflammatory functions. Recently, we demonstrated the immunoregulatory role played by PEDF in dry eye disease (DED) by suppressing the maturation of antigen-presenting cells at the ocular surface following exposure to the desiccating stress. In this study, we evaluated the effect of PEDF on the immunosuppressive characteristics of regulatory T cells (Tregs), which are functionally impaired in DED. In the presence of PEDF, the in vitro cultures prevented proinflammatory cytokine (associated with type 17 helper T cells)-induced loss of frequency and suppressive phenotype of Tregs derived from normal mice. Similarly, PEDF maintained the in vitro frequency and enhanced the suppressive phenotype of Tregs derived from DED mice. On systemically treating DED mice with PEDF, moderately higher frequencies and significantly enhanced suppressive function of Tregs were observed in the draining lymphoid tissues, leading to the efficacious amelioration of the disease. Our results demonstrate that PEDF promotes the suppressive capability of Tregs and attenuates their type 17 helper T-cell-mediated dysfunction in DED, thereby playing a role in the suppression of DED.
Gagan Kalra, Parul Ichhpujani, Sahil Thakur, Rohan Bir Singh, Urvashi Sharma, and Suresh Kumar. 2021. “A pilot study for smartphone photography to assess bleb morphology and vasculature post-trabeculectomy.” Int Ophthalmol, 41, 2, Pp. 483-490.Abstract
PURPOSE: The current grading systems used for bleb morphology assessment in patients post-trabeculectomy are based on standardized slit-lamp photographs and anterior segment imaging devices. The lack of availability of these expensive and non-portable devices in resource-deficient settings is a significant deterrent in their widespread utilization for proper post-operative management. The rapidly evolving utilization of smartphone photography has significantly benefited diagnostics of posterior segment disorders and is now being increasingly utilized for monitoring anterior segment pathologies as well as post-surgical course. In this study, we study a novel use of smartphones for bleb photography for assessing the morphological characteristics as vascularity and microcysts. METHODS: In this pilot, observational study, we compared the trabeculectomy bleb images of five subjects, obtained by iPhone X (dual lens) and iPhone 6S (single lens). We captured two image sets with both smartphones first with a focussed torchlight and then with a built-in flash video light. RESULTS: The images resulting from the newer iPhone X were substantially superior than those from iPhone 6S. For the 12-megapixel dual-camera set-up on the iPhone X, the 1 × lens resulted in better images than the 2 × lens with contrast and overall clarity of the area of interest. While the macro-lens attachment had promising results at 1 × zoom, there is no added advantage of the macro-lens attachment as it resulted in considerable loss of image quality at twice the zoom. Using a 20 D lens helped attain higher magnification and better framing as it reduced the focussing distance needed to get sharp images. The images obtained from both smartphones were of higher quality when illuminated from an external source when compared to the native iPhone flash due to even exposure and fewer autofocus artefacts. CONCLUSION: Analyses of all image sets showed that the current generation in-built camera app on IOS and newer iPhone camera optics resulted in high-quality images of the ocular surface with high magnification without any loss in clarity.
Vasudha Sharma, Sehajbir Dhaliwal, and Rohan Bir Singh. 2021. “Psychological and Physical Implications of COVID-19 on School Children in India.” Asia Pacific Journal of Public Health, 33, 5, Pp. 672-673.
Nai-Wen Fan, Thomas H Dohlman, William Foulsham, Matthew McSoley, Rohan Bir Singh, Yihe Chen, and Reza Dana. 2021. “The role of Th17 immunity in chronic ocular surface disorders.” Ocul Surf, 19, Pp. 157-168.Abstract
Th17 cells have been implicated in the pathogenesis of numerous inflammatory and autoimmune conditions. At the ocular surface, Th17 cells have been identified as key effector cells in chronic ocular surface disease. Evidence from murine studies indicates that following differentiation and expansion, Th17 cells migrate from the lymphoid tissues to the eye, where they release inflammatory cytokines including, but not limited to, their hallmark cytokine IL-17A. As the acute phase subsides, a population of long-lived memory Th17 cells persist, which predispose hosts both to chronic inflammation and severe exacerbations of disease; of great interest is the small subset of Th17/1 cells that secrete both IL-17A and IFN-γ in acute-on-chronic disease exacerbation. Over the past decade, substantial progress has been made in deciphering how Th17 cells interact with the immune and neuroimmune pathways that mediate chronic ocular surface disease. Here, we review (i) the evidence for Th17 immunity in chronic ocular surface disease, (ii) regulatory mechanisms that constrain the Th17 immune response, and (iii) novel therapeutic strategies targeting Th17 cells.
Rohan Bir Singh, Anna Marmalidou, Afsaneh Amouzegar, Yihe Chen, and Reza Dana. 2020. “Animal models of high-risk corneal transplantation: A comprehensive review.” Exp Eye Res, 198, Pp. 108152.Abstract
Over the past century, corneal transplantation has become the most commonly performed allogeneic solid tissue transplantation. Although more than 80% of the corneal transplantations have favorable outcomes, immune-mediated rejection continues to be the major cause of failure in well over 50% of graft recipients that have inflamed and vascularized host beds. Over the past two decades, the progress in our understanding of the immunological pathways that mediate graft rejection has aided in the development of novel therapeutic strategies. In order to successfully test the efficacy of these interventions, it is essential to model the immunological processes occurring as a consequence of corneal transplantation. Herein, we have comprehensively reviewed the established animal models used for replicating the immunopathological processes causing graft rejection in high-risk corneal transplantation settings. We have also discussed the practical and technical differences, as well as biological and immunological variations in different animal models.
Parul Ichhpujani, Tanu Singh, Sahil Thakur, Rohan Bir Singh, and Suresh Kumar. 2020. “Assessing glaucoma deterioration using Spaeth/Richman contrast sensitivity test.” Ther Adv Ophthalmol, 12, Pp. 2515841420977412.Abstract
Purpose: To assess changes in the central and peripheral contrast sensitivity in severe primary open-angle glaucoma (POAG) patients using a computer-based Spaeth/Richman contrast sensitivity test (SPARCS) over a period of 24 months. Methods: Our pilot, observational study included 15 patients (30 eyes) with severe POAG. Visual acuity, intraocular pressure, number of anti-glaucoma drugs, visual fields, and SPARCS score were recorded at first visit and at 12 and 24 months. Results: We observed changes in mean deviation (MD) from -19.37 ± 5.04 to -20.63 ± 4.07, mean pattern standard deviation (PSD) from 11.49 ± 2.61 to 11.35 ± 2.01, and mean SPARCS score from 54.97 ± 15.66 to 53.50 ± 16.42. We found no statistically significant difference between visual field parameters and SPARCS scores associated with the number or type of prescribed anti-glaucoma drugs. Spearman's correlation coefficient of SPARCS at baseline (SPARCS1) MD at baseline (MD1) was 0.274 ( = 0.142) and SPARCS1 PSD at baseline (PSD1) was -0.163 ( = 0.389). The correlation coefficient between SPARCS at 12 months (SPARCS2) MD (MD2) at the same time point was computed to be 0.391 ( = 0.03), whereas SPARCS2 PSD at 12 months was -0.212 ( = 0.262). Similarly, we found the coefficient to be 0.336 ( = 0.069) for SPARCS3 (SPARCS at 24 months) MD3 (MD at 24 months) and 0.242 ( = 0.197) for SPARCS3 PSD3 (PSD at 24 months). Correlation coefficients between SPARCS1/2, SPARCS1/3, MD1/2, MD1/3 PSD1/2, and PSD1/3 were 0.856, 0.865, 0.748, 0.722, 0.497, and 0.562, respectively ( < 0.001). MD changed by 9.46% ± 12.73%, PSD by 0.64% ± 14.03%, and average SPARCS by 3.31% ± 12.73% over 24 months. Conclusion: The data from our study indicate the utilitarian application of SPARCS, an inexpensive and readily available tool for monitoring functional deterioration in cases with advanced glaucomatous damage, especially in resource-poor settings. Furthermore, it is a useful and reliable alternative to the imaging modalities where retinal nerve fiber layer measurement can be erroneous in advanced cases secondary to the floor effect.
Rohan Bir Singh, Ann Yung, Giulia Coco, Shruti Sinha, Thomas H Dohlman, Jia Yin, and Reza Dana. 2020. “Efficacy and retention of silicone punctal plugs for treatment of dry eye in patients with and without ocular graft-versus-host-disease.” Ocul Surf, 18, 4, Pp. 731-735.Abstract
PURPOSE: To examine the retention rates and efficacy of silicone punctal plugs for the treatment of dry eye disease (DED) in patients with ocular graft-versus-host-disease (oGVHD) in comparison to dry eye disease due to non-oGVHD etiologies. METHODS: We reviewed the case-records of 864 consecutive patients with DED who were symptomatic despite topical therapy and had silicone punctal plugs placed over an eight-year- period at a single academic center. We compared plug retention rates in oGVHD and non-oGVHD DED patients using Kaplan-Meier analyses. Furthermore, we analyzed changes in objective ocular surface parameters including tear breakup time (TBUT), Schirmer's test, and corneal fluorescein staining (CFS) score in plug-retaining patients at two-, six- and twelve-month follow-up. RESULTS: Median age of dry eye patients was 58 years, and 606 (70%) of patients were women. In the cohort, 264 (31%) patients were diagnosed with oGVHD. Plug retention was significantly lower in oGVHD-DED patients compared to non-oGVHD-DED patients (p < 0.0001). We observed significant improvement in CFS scores in plug retaining-oGVHD and non-oGVHD DED patients at all time points. Tear break-up time was significantly prolonged at six- and twelve-months follow-up in non-oGVHD patients, whereas significant change in TBUT in oGVHD patients was recorded only at twelve months post plug placement. Schirmer's score improved significantly in plug retaining-non-oGVHD DED patients at six- and twelve-months follow-up, however no significant change was observed in Schirmer's score in oGVHD DED patients. CONCLUSIONS: An improvement in ocular surface disease parameters was observed in both plug-retaining oGVHD and non-oGVHD DED patients. However, a majority of oGVHD DED patients spontaneously lost their punctal plugs within 90 days of placement. Therefore, regular follow-up after plug placement is recommended to detect plug loss and ensure adequate disease control.