Beyond visual acuity: BostonSight's current research into mental health and lid disease

BostonSight, the nonprofit organization behind the Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) device, is expanding its clinical research agenda beyond traditional ophthalmic endpoints — examining how ocular surface disease and its treatment intersect with patient quality of life, mental health and comorbid conditions that can undermine treatment outcomes.

Two areas of active investigation stand out. The first involves the role of Demodex blepharitis in PROSE device wearers. BostonSight is investigating whether treating the mite-driven lid margin inflammation that defines Demodex blepharitis can improve the comfort and performance of PROSE devices in patients who struggle with fogging, discomfort or limited wear time. The study is supported by a research grant from Tarsus Pharmaceuticals, maker of Xdemvy, the first FDA-approved treatment for Demodex blepharitis.

The second area addresses something less commonly tracked in eye care clinical trials: mental health. BostonSight is formally studying whether PROSE treatment produces measurable improvements in depression severity, using the PHQ-9 questionnaire alongside standard ocular surface and visual function measures. The research formalizes what clinicians at BostonSight say they observe routinely — that for patients who have spent years in pain and isolation from severe ocular surface disease, effective treatment can produce changes that extend well beyond visual acuity.

In this Q&A, Daniel C. Brocks, MD, BostonSight chief medical officer, discusses both studies, the patients they serve, and what the broader eye care community may be missing.

Transcript

Edited lightly for clarity and length.

Demodex blepharitis in scleral lens wearers

What prompted BostonSight to investigate the relationship between Demodex blepharitis and PROSE device wearers specifically?

Daniel C. Brocks, MD: Demodex blepharitis causes lid and ocular irritation, discomfort, ocular surface inflammation and poor tear film – all of which can interfere with the performance and tolerance of a PROSE device on the eye. Some patients wearing PROSE will struggle with such things as vision fogging, blurring, discomfort, redness, or limited hours of wear time. Our hypothesis is that if you can address the underlying Demodex blepharitis, this will reduce ocular surface inflammation and improve tear quality and function, in turn resulting in improved PROSE wearing comfort and performance. This hypothesis and a study protocol to investigate was presented to Tarsus Pharmaceuticals, Inc., who were willing to support the investigation through a research grant.

How do you currently screen PROSE patients for Demodex blepharitis, and do you feel awareness of this comorbidity is adequate among scleral lens fitters broadly?

Brocks: Currently, the best way to screen patients for Demodex blepharitis is to evaluate their presenting symptoms and examine their lids and lashes on a thorough slit lamp examination. Lash collarettes (crusty, waxy rings of waste that build up around the base of the eyelashes) are the best current surrogate marker for active Demodex blepharitis. Removing lashes and examining for Demodex at a microscope is not efficient or necessary. It is helpful to grade the level of collarettes, as signs often relate nicely to the grading level and this is a reliable end point to monitor for medication (Xdemvy) effect. We use the same grading scale as implemented in the FDA trials SATURN-1 and SATURN-2. (The SATURN-1 and SATURN-2 FDA clinical trials successfully evaluated the safety and efficacy of TP-03, which led to the FDA approval of Xdemvy.)

The awareness and importance of diagnosing blepharitis and more specifically Demodex blepharitis in scleral lens and PROSE wearers is unfortunately still underappreciated in the ophthalmic and optometric community. We feel aggressively treating active lid margin inflammation is an extremely important component in order to achieve optimized scleral lens tolerance and functionality.

The effect of PROSE treatment on mental health

What clinical observations led your team to formally investigate the mental health dimension of PROSE treatment — were patients spontaneously reporting psychological changes alongside visual improvement?

Brocks: This is a very important question and an often overlooked or underappreciated part of caring for ocular surface disease patients. The often-dramatic effect that the improvement of vision, improvement of ocular comfort, and improvement of ocular health with PROSE can have on mental health is an aspect of our care experienced on a regular basis. However, in ophthalmic and optometric communities, we have seen this aspect of PROSE and scleral lens care get little attention, with the general focus typically being on standard ophthalmic care parameters, such as BCVA or corneal staining. But the patient will often comment on the life changing effect of PROSE treatment as it relates to their happiness, particularly in the way it has allowed them to return to the activities of daily life they enjoy and return to doing and being who they want to be.

For some of our patients, such as ocular GVHD patients, the experience of putting on their first PROSE device in the exam room can be highly emotional for both them and their families as well as any students observing. The effect of almost immediate pain relief after years of suffering can bring about an acute dramatic change in demeanor (and smile) and we hypothesize a quantifiable mental health effect.

Which standardized questionnaires are being used in the study, and what domains of mental health are you primarily measuring?

Brocks: We are measuring mental health primarily with the PHQ-9 questionnaire. This provides a valuable snapshot and is generally considered one of the most reliable and most clinically relevant depression severity questionnaires. Alongside, we are evaluating ocular surface symptoms with the OSDI and visual functioning with VFQ-25 to see how changes in mental health may relate to specific scores on vision centered questionnaires.

PROSE patients often come to BostonSight after years of failed treatments — do you believe the mental health burden in this population is underappreciated by the broader eye care community?

Brocks: Unfortunately, I do believe the mental health burden in ocular surface disease patients is generally underappreciated in the broader eye care community. This lack of recognition is a true and serious problem. Often, a long, drawn-out, stepwise approach to ocular surface care can lead to years of unnecessary suffering for patients. This exacerbates mental health adversity, particular in those with affective mood disorders.

Much of the issue comes from this important associated problem- though academically speaking ophthalmologists and optometrist may be educated on this important mental health association, few are afforded the time or given the tools to properly integrate diagnosing, monitoring, addressing, and referring mental health issues for appropriate services. We do our part as eye care providers to treat ocular surface disease- and as a result I believe we meaningfully change mental health. But it is rarely explicitly addressed or monitored in the exam room in a standardized systematic way.

Regardless of the study outcome, what would you want referring clinicians to understand about the psychological profile of the patients who typically need PROSE treatment?

Brocks: There are many disease states that PROSE can address, particularly in the moderate to severe OSD categories, which have the highest association with mental health challenges. This can include patients with such pathology as dry eye syndrome, Sjogren Disease, chemical burns, SJS, OCP, exposure keratopathy, neurotrophic keratitis ,and more. First and foremost, we would stress- if you see a patient suffering and standardized management doesn’t seem to be moving the needle and your clinical acumen tells you that it is unlikely for standard interventions to help – refer the patient for PROSE or scleral lenses as appropriate. The effects can be dramatic for the ocular surface, but even more importantly for their life and livelihood. There is no reason to hit every step in the dry eye or ocular surface playbook if your clinical judgment tells you it is unlikely to be successful. Move treatment forward efficiently using your expertise of disease mechanism, drug and device targets, and years of experience knowing who may or may not respond to which treatment. It is no exaggeration to say that we are referred patients contemplating suicide due to years of suffering pain and isolation from ocular surface disease, whose experience with PROSE, and the relief afforded to them, results in a new active and fulfilling life with dramatic mental health improvement.