Veeral Sheth, MD, MBA, FASRS, FACS

Retinal Fluid and Visual Acuity After PDS Ranibizumab with Veeral Sheth, MD, MBA

2025 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting

, Veeral Sheth, MD, MBA, director of clinical research at the University of Retina and Macula Associates and clinical assistant professor at the University of Illinois, presented a volumetric analysis of retinal fluids from the Archway phase 3 trial evaluating the Port Delivery System (PDS) with ranibizumab in patients with 

neovascular age-related macular degeneration

The post hoc analysis used a pre-trained deep learning model to segment subretinal and intraretinal fluid (SRF and IRF) on optical coherence tomography scans.

“What our model did was get rid of the noise, because with fluctuations, you get a lot of noise,” Sheth told 

. “And one of the key things is filtering out some of that noise. If you leave it to us just individually plot it out, it can be very labor-intensive, very cumbersome. This is where advancements in technology have really helped us. We can use these algorithms to get rid of the noise, and then we can really start looking at deviations in a slightly different way.”

In the phase 3 Archway trial, patients were randomized 3:2 between the PDS with ranibizumab 100 mg/mL, with established 24-week refills (PDS Q24W) and ranibizumab 0.5 mg intravitreal injection every 4 weeks (RBZ Q4W). Sheth’s study highlighted eyes with imaging data of quality adequate for volumetric analysis of retinal fluid. A variability metric robust to absent values and outliers was calculated for the central subfield thickness (CST), volume of SRF and IRF in the central subfield for each eye.

Sheth and colleagues found no significant difference in fluid fluctuation from baseline to week 96 across both treatment arms (PDS Q24W, RBZ Q4W, mean +/- [standard deviation] SD, CST (µm): 5.2 +/- 5.1, 4.9 +/- 6.5l; IRF (nL): 0.4 +/- 2.0, 0.5 +/- 2.6; SRF (nL): 2.1 +/- 3.8, 1.4 +/- 3.2, all 

When the team categorized by IRF fluctuation, best-corrected visual acuity (BCVA) was substantially higher (

 <.001) in eyes in the lowest quartile than in the highest (lowest vs highest IRF fluctuation quartile, mean +/-SD, BCVA (letters): 76 +/- 10.8, 68.0 +/- 17.0). However, when segmented by SRF fluctuation, median BCVA was not significantly different (

 >.05) in eyes in the lowest and highest quartile (lowest vs highest SRF fluctuation quartile, mean +/- SD, BCVA (letters): 72.9 +/- 14.3, 74.8 +/- 11.0).

Sheth and colleagues’ results showed that BCVA is significantly higher in eyes with less IRF fluctuation than with more.

“I think that really helps support some of the data, the building of a body of evidence that intraretinal fluid fluctuations or even residual intraretinal fluid really does matter, and has an impact on patients’ vision,” Sheth said. “I think we should look closely at intraretinal fluid in patients visit to visit and really look for treatments that address that variability or fluctuation in the intraretinal fluid.”

Sheth, V, et al. Volumetric analysis of retinal fluids in Archway phase 3 trial of the Port Delivery System with ranibizumab (PDS) in patients with nAMD. Abstract presented at Association for Research in Vision and Ophthalmology in Salt Lake City, UT, from May 3 - May 8, 2025.

Videos

A post hoc analysis of trial data reveals the effects of intraretinal fluid on best-corrected visual acuity in patients after port delivery system treatment for nAMD.

Retinal Fluid and Visual Acuity After PDS with Ranibizumab, With Veeral Sheth, MD, MBA

New Insight: Exploring ENCELTO for MacTel with Rich Small, CEO of Neurotech

In this episode of New Insight, host Veeral Sheth, MD, MBA, director of clinical research at University Retina and Macula Associates, speaks with Rich Small, chief executive officer of Neurotech, about the recent 

 approval of revakinagene taroretcel-lwey (ENCELTO), a groundbreaking encapsulated cell therapy for 

This approval marked the first and only FDA–approved treatment for MacTel, a neurodegenerative disease of the retina that can cause progressive and irreversible vision loss.

“Today marks an extraordinary milestone for patients, the retina community, and Neurotech,” Small said in a statement. “I would like to express my gratitude to clinical study participants, clinical investigators and their teams, and the entire Neurotech organization who have helped make this a reality.”

Speaking with Sheth, Small recounted the long journey of Neurotech, which began in 2007, emphasizing the perseverance required to bring ENCELTO to market. He detailed his transition from Chief Financial Officer to CEO in 2016 and highlighted his team’s commitment, many of whom have been with the company for over a decade.

The conversation explored the scientific foundation of ENCELTO, which uses genetically modified cells to release neurotrophic factors that protect photoreceptors in the retina. Unlike previous treatments that relied on best corrected visual acuity (BCVA) as a clinical endpoint, ENCELTO’s approval was enabled by advancements in imaging technology that allowed for direct measurement of photoreceptor health. Small explained how Neurotech was pivotal in shifting FDA standards to accept these structural endpoints, paving the way for future therapies targeting slow-progressing retinal diseases.

Sheth and Small discussed the ideal patient profile for ENCELTO, noting that early intervention is key to preserving vision in MacTel patients. Small describes the treatment’s durability, citing cases where implants remained viable for approximately 14 years. He also outlined the surgical implantation process, emphasizing its straightforward nature and the company’s focus on proper physician training.

With ENCELTO’s approval secured, Small indicated the next step is widespread adoption, introducing 

 as a patient service hub designed to streamline diagnosis, treatment, and access to care.

Sheth underscored the significance of this approval, noting that for the first time, clinicians have an option for patients who previously had no treatment alternatives. Reflecting on the impact of perseverance in biotech innovation, and the hope ENCELTO brings to patients, Small expressed pride in Neurotech’s achievement and excitement about delivering this novel therapy to those in need.

Every episode of New Insight is available on HCPLive.com. Watch full episodes on our YouTube channel and listen wherever you get your podcasts.

Podcasts

Veeral Sheth, MD, is joined by the CEO of Neurotech to discuss the historic approval of revakinagene taroretcel (ENCELTO) for macular telangiectasia type 2.

New Insight: A Deep Dive into the Oculis Pipeline with Riad Sherif, MD

 Riad Sherif's Journey from Physician to CEO


 Challenges of Balancing Medical and Business Roles


 Oculis' Portfolio and Recent Developments


, host Veeral Sheth, MD, MBA, director of clinical research at University Retina and Macula Associates, spoke with Riad Sherif, MD, CEO of Oculis, about the company's groundbreaking advancements in 

Sherif shared his journey from physician to industry leader, detailing his experiences at Sanofi, Novartis, and Alcon before transitioning to venture investment and eventually leading Oculis. He highlighted how his medical background informs his leadership approach, emphasizing a patient-first philosophy that drives innovation and sustainable growth in drug development.

The discussion delved into Oculis' clinical pipeline, particularly OCS-05, a neuroprotective agent demonstrating promising results in acute optic neuritis. The Phase 2 ACUITY trial showed that OCS-05 preserved retinal ganglion cells (RGCs), reduced axonal loss, and improved low-contrast visual acuity. Importantly, patients receiving OCS-05 experienced significantly fewer multiple sclerosis relapses, suggesting broader neuroprotective potential. Administered intravenously alongside corticosteroids, the therapy could represent a paradigm shift in preserving vision in acute optic neuritis and beyond.

Sheth and Sherif also explored Oculis' lead candidate, OCS-01, a topical treatment for diabetic macular edema (DME) that uses an OPTIREACH® formulation of high-concentration dexamethasone to penetrate the retina. With two ongoing Phase 3 trials (DIAMOND 1 and 2), OCS-01 has the potential to offer a non-invasive alternative or adjunct to intravitreal injections, expanding treatment options for patients with DME. Additionally, Oculis' OCS-02, a TNF inhibitor for dry eye disease (DED), integrates a biomarker-driven precision medicine approach, ensuring targeted therapy for responders and potentially revolutionizing dry eye treatment.

Sherif provided insight into Oculis' international operations, highlighting its dual listings in the US and Iceland, the latter a strategic decision to engage Icelandic investors and maintain strong ties to the company’s research roots. He underscored the importance of assembling a high-caliber, mission-driven team to ensure successful execution in an unpredictable scientific landscape.

Looking ahead, Sherif noted that Oculis is focused on executing its clinical programs, particularly finalizing patient randomization in the DIAMOND trials, advancing precision medicine for inflammation, and expanding indications for OCS-05 in neuroprotection. In particular, he envisioned OCS-05 as a potential game-changer addressing significant unmet needs in ophthalmology by preserving vision and improving the quality of life for patients facing vision-threatening diseases.

Every episode of New Insight is available on HCPLive.com. Watch full episodes on our

and listen wherever you get your podcasts. Please direct all podcast-related inquiries to producer Connor Iapoce (ciapoce@mjhlifesciences.com)!

Veeral Sheth, MD, is joined by the CEO of Oculis to discuss the company's ophthalmic pipeline, including OCS-01 for DME and OCS-05 for acute optic neuritis.

New Insight: A Look at Qlosi for Presbyopia with Elad Kedar, MBA

 Elad Kedar's Background and Company Growth

 Transition from Product Development to Team Building

In this episode of New Insight, host Veeral Sheth, MD, MBA, director of clinical research at University Retina and Macula Associates, explored the approval and impending launch of Qlosi (pilocarpine HCL ophthalmic solution) 0.4%, a groundbreaking pharmacologic option for managing 

, with Elad Kedar, MBA, chief executive officer of Orasis Pharmaceuticals.

A condition that affects nearly all adults as they age, presbyopia is characterized by the gradual loss of near vision due to reduced lens elasticity. Sheth and Kedar highlighted the significance of finding non-invasive treatment options for this pervasive issue, given the limitations of traditional solutions like reading glasses or surgical interventions.

In October 2023, the US Food and Drug Administration (FDA) approved Qlosi, a preservative-free, low-dose eye drop for presbyopia, based on strong efficacy, safety, and tolerability data reported in the pivotal Phase 3 NEAR-1 and NEAR-2 clinical trials. On Day 8, patients treated with Qlosi achieved statistically significant ≥3-line gain in distance-corrected near visual acuity (DCNVA) and no loss of ≥1-line in distance visual acuity.

Sheth and Kedar delved into Qlosi’s innovative mechanism of action, emphasizing how it leverages a unique pharmacologic approach to improve near vision. By modulating pupil dynamics, Qlosi enhances the depth of focus, effectively allowing patients to perform near-vision tasks without additional aids. Together, Sheth and Kedar walked through the drug’s clinical development journey, highlighting his journey through the founding of Orasis and the company’s name in Greek, meaning “good vision or sight.”

The discussion included insights into the populations most likely to benefit from Qlosi and the practical considerations for prescribing. Sheth offered a nuanced take on how this therapy could fit into the broader landscape of presbyopia management, addressing questions about patient education, adherence, and expectations.

Sheth also shared his perspective on the potential impact of Qlosi on clinical practice, noting that its ease of use and non-invasive nature could appeal to both patients and providers. He reflected on how treatments like Qlosi are part of a broader trend toward personalized medicine, focusing on solutions that improve the quality of life for aging populations.

This episode concluded with a thoughtful look at future research directions and the impending launch of Qlosi. Expected soon, Kedar expressed an interest in sharing more details on the product and its position in the presbyopia treatment landscape once the drug comes to market.

Every episode of New Insight is available on HCPLive.com. Watch full episodes on our 

 and listen wherever you get your podcasts. Direct all podcast-related inquiries to show producer Connor Iapoce (ciapoce@mjhlifesciences.com) and keep an eye out for more from New Insight!

In this episode, Veeral Sheth, MD, is joined by the CEO of Orasis Pharmaceuticals to discuss Qlosi, a preservative-free, low-dose eye drop FDA-approved for presbyopia.

Veeral Sheth, MD, MBA, FASRS, FACS

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