Research Roundup: Essential 2022 Studies You May Have Missed

Across the ophthalmic literature, major advances are giving ophthalmologists new options for treatment and success. Credit: Getty Images
In 2022, researchers in ophthalmology delivered pioneering studies that have long-term implications in glaucoma, retinal, uveitis, and oncological care.

Ophthalmology Advisor publishes articles on a plethora of academic research from across the globe in an effort to keep clinicians abreast of the most vital discoveries affecting their discipline. But, while we publish articles on close to 1000 studies per year (it’s true, we did the math!), it’s still not enough to capture all the magnificent research relevant to ophthalmology every year. We don’t want to dwell on the past, but there are a few published studies affecting the field that we skipped the first time around and we’d be remiss not to acknowledge them now. 

Keeping up with the latest findings is an ongoing conversation. If you’ve been following along through 2022, you’ve certainly got enough to talk about — but by adding these crucial findings, you can start 2023 off right, with a more complete view of what last year has added to the conversation. 

Glaucoma

A subspeciality of ophthalmology with particularly robust literature, glaucoma monitoring and treatment was particularly active in 2022. In the last 12 months, researchers have shown the benefits of standalone minimally invasive glaucoma surgeries (MIGS), the applicability of optical coherence tomography angiography (OCT-A) in long-term disease monitoring, and new contraindications for some patients. 

But glaucoma is an amorphous topic with several subtopics branching off from it. While most research focuses on primary open-angle glaucoma (POAG), subtopics such as primary angle closure glaucoma (PACG) and Charles Bonnet syndrome affect many patients. Just how many patients with POAG are affected by Charles Bonnet syndrome was, in fact, the topic of a May 2022 study — Charles Bonnet syndrome in patients with open-angle glaucoma: prevalence and correlation to visual field loss? It turns out that a large group of patients with POAG — 7.1% — experience this type of hallucination. The study also shows that patients are at increased risk of experiencing Charles Bonnet syndrome if they have a combination of advanced visual field loss and low best-corrected visual acuity. The study also shows that more than a quarter of patients with Charles Bonnet syndrome did not tell anyone about their hallucinations. Half of those patients experienced concomitant hearing difficulties.1

It goes without saying that surgical treatment is infrequently applied for patients who have yet to develop a disease. But that’s what researchers from the Republic of Singapore considered last year when they evaluated the use of prophylactic laser peripheral iridotomy (LPI) for patients with PACG. The Ophthalmology publication, The Singapore asymptomatic narrow angles laser iridotomy study, shows that, in a 5 year study, asymptomatic eyes with suspected PACG that were prophylactically treated with LPI halved their risk of developing either PACG or POAG.2 

Retina and Uveitis 

Retina care advanced significantly in 2022, especially as it pertains to the growing number of anti-vascular endothelial growth factor (anti-VEGF) options. Research from 2022 shows that, of the newer options, faricimab can reduce the treatment burden and may even have an effect on treatment resistant cases of diabetic macular edema (DME). But that doesn’t mean that the original trio of anti-VEGF agents aren’t still finding applications. Aflibercept monotherapy or bevacizumab first for diabetic macular edema, a New England Journal of Medicine article published in August, specifically asked: can switching between aflibercept to bevacizumab improve outcomes for patients who do not respond satisfactorily to initial treatment for DME? That study looked at 312 eyes of 270 patients at 54 clinical sites, with 158 eyes assigned to receive aflibercept only, and 154 to receive bevacizumab first. In 2 years, 70% of bevacizumab-first eyes were switched to aflibercept. For the most part, visual outcomes were similar, as were retinal central subfield thicknesses. But the report shows more serious adverse events in the aflibercept-monotherapy group (52%) than the bevacizumab-first group (36%) and more hospitalizations for adverse events (48% and 32%, respectively).3

In addition to anti-VEGF advancements, researchers are showing success with new protocols for corticosteroid therapies. In particular, a Japanese Journal of Ophthalmology publication issued in March shows that a combination of oral prednisolone and cyclosporine can manage Vogt–Koyanagi–Harada (VKH) disease, a type of uveitis, as effectively as corticosteroid pulse therapy, but with lower sunset glow fundus incidence, and a reduced risk of recurrence or worsening, or cataract development. The study — Comparison of combination therapy of prednisolone and cyclosporine with corticosteroid pulse therapy in Vogt-Koyanagi-Harada disease — may even have implications for types of uveitis outside of VKH, with the regimen being a potential alternative to high-dose corticosteroids and their risks.

Ophthalmic Oncology

Conjunctival melanomas are uncommon, but may be increasing (particularly in patients with White ethnicities), according to Mutational landscape and outcomes of conjunctival melanoma, a study published in Ophthalmology in January, 2022, which took more than 20 years of patient data into account. The study identifies targetable mutations and molecular genetic pathways associated with metastasis. The researchers confirmed “a high frequency of previously documented BRAF and NRAS mutations and recently reported ATRX and NF1 mutations in conjunctival melanoma,” the study says. “An NRAS mutation implied increased risk for metastasis and death. Loss of ATRX and ALT may be early events in conjunctival melanoma development.” With this knowledge, physicians may consider adding mutational profiles of conjunctival melanoma tumors by next-generation sequencing to standard of care for these patients. This is particularly the case for patients with NRAS tumors, which can be stealthy in that they lack diffuse pigmentation, and yet, they are known for “aggressive behavior,” according to the report.  

An April Ophthalmology study, High-risk pathologic features based on presenting findings in advanced intraocular retinoblastoma, shows that a histopathology evaluation may help guide treatment. Using clinical — not pathological — features identified by the study, clinicians may have an objective biomarker for determining which patients with retinoblastoma are in a position to retain the globe, which require enucleation, and which are at metastatic risk and should undergo systemic preventive chemotherapy. These features include stage cT3c disease (characterized by iris neovascularization with glaucoma), cT3d (intraocular hemorrhage), and cT3e (aseptic orbital cellulitis). Tumor size classification was also relevant in that size groups 3 and 4 put patients at higher risk.

Ophthalmic research continues to march forward, giving physicians pathways to more precise surgical techniques, treatments that reduce patient burden, and, in some cases, sight-saving and even life-saving capabilities. With 2023 underway, Ophthalmology Advisor will stay on the beat and keep you apprised of all of these future developments.

References:

  1. Peters D, Molander S, Lomo T, Singh A. Charles Bonnet syndrome in patients with open-angle glaucoma: prevalence and correlation to visual field loss. Ophthalmol Glaucoma. 2022;5(3):337-344. doi:10.1016/j.ogla.2021.10.010
  2. Baskaran M, Kumar RS, Friedman S, et al. The Singapore asymptomatic narrow angles laser iridotomy study: five-year results of a randomized controlled trial. Ophthalmol. 2022;129(2):147-158. doi:10.1016/j.ophtha.2021.08.017
  3. Jhaveri CD, Glassman AR, Ferris FL, et al. Aflibercept monotherapy or bevacizumab first for diabetic macular edema. N Engl J Med. 2022;387:692-703. doi:10.1056/NEJMoa2204225
  4. Ono T, Goto H, Sakai T, et al. Comparison of combination therapy of prednisolone and cyclosporine with corticosteroid pulse therapy in Vogt-Koyanagi-Harada disease. Jpn J Ophthalmol. 2022;66(2):119-129. doi:10.1007/s10384-021-00878-w
  5. Lally SE, Milman T, Orloff M, et al. Mutational landscape and outcomes of conjunctival melanoma. Ophthalmol. 2022;129(6):679-693. doi:10.1016/j.ophtha.2022.01.016
  6. Tomar AS, Finger P, Gallie B, et al. High-risk pathologic features based on presenting findings in advanced intraocular retinoblastoma. Ophthalmol. 2022;129(8):923-932. doi:10.1016/j.ophtha.2022.04.006