Improved grading scales for oncology drugs causing ocular adverse events

A new consensus report¹ published in JAMA Ophthalmology described new experimental oncology drug–related ocular adverse event grading scales that were compiled with the goals of achieving conciseness and the ability to provide clear drug-dose-modification recommendations compared with the previous ocular Common Terminology Criteria for Adverse Events (CTCAE) scale, according to the study authors. Neel D. Pasricha, MD, from the Department of Ophthalmology and the Francis I. Proctor Foundation, University of California, San Francisco, was the lead study author.

“Robust reporting of ocular adverse events is important to maintain patient safety and guide the development of novel efficacious drugs,” the panel members commented.

They cited corneal pseudomicrocysts as a common ocular adverse event associated with the use of antibody-drug conjugates (ADCs) that can lead to blurred vision and eye pain in up to 90% of patients on select ADC therapy.^2,3

Background

Before the consensus panel, which was comprised of ophthalmologists and oncologists, began their evaluation, the then-current ocular CTCAE scale was described as having limitations, in that it mixed eye signs with symptoms and did not provide standardized clinical photographs or experimental oncology drug-dose modification recommendations, according to the study authors.

The consensus panel explained that the investigation into ADCs is a very active area in that there currently are 12 FDA-approved ADCs that comprise a class of targeted cancer therapies,^4,5 and there are more than 160 in clinical trials.^6,7

In light of the potential numbers of ADCs that may enter clinical practice, the authors noted the importance of the accurate grading of ADC drug-related ocular adverse events and timely communication between eye care clinicians and oncologists to patient quality of life.⁸

The limitations of the CTCAE scale include ambiguous terms such as "dry eye" and "keratitis"; mixed signs and symptoms, for example, keratitis grades include visual acuity, objective clinical examination findings, and subjective patient symptoms; and the absence of clinical photographs and recommended dose modifications of the experimental oncology drugs.

The work of the consensus panel

The investigators pointed out the importance of developing “improved ocular adverse event grading scales to reliably evaluate and grade ocular adverse events in patients on experimental oncology drug therapy and to provide clear drug dose modification recommendations,” they stated.

The panel members determined that the latest scales were “ambiguous with unreliable ocular adverse event grading leading to unclear recommendations for experimental oncology drug-dose modifications.”

The members reviewed the literature and relied on their knowledge of oncology drug-related adverse events to form a consensus on new ocular adverse event grading scales. “Efforts were focused on using unambiguous terms, separating signs and symptoms, using representative clinical photographs when indicated, and providing clear experimental drug dose modification recommendations. Multiple virtual meetings were held, with each member having the opportunity to review the data and comment on the collective working group recommendations,” they explained.

What changes did the panel implement?

The panel members developed 6 new oncology drug-related ocular adverse event grading scales for use in antibody-drug conjugate clinical trials that covered visual acuity, eye symptoms, cornea, conjunctiva/sclera, anterior chamber, and retina/posterior segment. The scales also include experimental drug-dose modification recommendations.

Compared to the previous CTCAE version, the panelists reported that the “new ocular adverse event grading scales provided 4 main improvements,” ie, use of the following: clear anatomic terms such as corne

a and conjunctiva/sclera, separate signs and symptoms such as visual acuity grades for vision changes and cornea grades for objective corneal clinical findings, representative clinical photographs if applicable, and recommendations for experimental oncology drug dose modifications.

The panel members concluded, “Use of these ocular adverse event grading scales may allow for more objective and consistent incidence measurements of ocular adverse events throughout clinical trials and postmarketing, potentially facilitating safe testing of novel agents that may cause eye toxicity.”

References

1. Pasricha ND, Kim SK, Farooq AV, et al. Multicenter interspecialty consensus on experimental oncology drug–related ocular adverse event reporting. JAMA Ophthalmol. 2025; published online December 4. doi:10.1001/jamaophthalmol.2025.3159

2. Farooq AV, Degli Esposti S, Popat R, et al. Corneal epithelial findings in patients with multiple myeloma treated with antibody-drug conjugate belantamab mafodotin in the pivotal, randomized, DREAMM-2 study. Ophthalmol Ther. 2020;9:889-911. doi:10.1007/s40123-020-00280-8

3. Lindgren ES, Yan R, Cil O, et al. Incidence and mitigation of corneal pseudomicrocysts induced by antibody-drug conjugates (ADCs). Curr Ophthalmol Rep. 2024;12:13-22. doi:10.1007/s40135-024-00322-5

4. Naito K, Takeshita A, Shigeno K, et al. Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines. Leukemia. 2000;14:1436-1443. doi:10.1038/sj.leu.2401851

5. Maecker H, Jonnalagadda V, Bhakta S, Jammalamadaka V, Junutula JR. Exploration of the antibody-drug conjugate clinical landscape. MAbs. 2023;15:2229101. doi:10.1080/19420862.2023.2229101

6. Barker AD, Sigman CC, Kelloff GJ, Hylton NM, Berry DA, Esserman LJ. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther. 2009;86:97-100. doi:10.1038/clpt.2009.68

7. Esserman LJ, Woodcock J. Accelerating identification and regulatory approval of investigational cancer drugs. JAMA. 2011;306:2608-2609. doi:10.1001/jama.2011.1837

8. Craig JP, Alves M, Wolffsohn JS, et al. TFOS lifestyle report executive summary: a lifestyle epidemic—ocular surface disease. Ocul Surf. 2023;30:240-253. doi:10.1016/j.jtos.2023.08.009