Frequency and Patterns of Hearing Dysfunction in Patients Treated With Teprotumumab
Keen JA, Correa T, Pham C, et al. Frequency and Patterns of Hearing Dysfunction in Patients Treated with Teprotumumab. Ophthalmology. 2024;131(1):30-36. doi:10.1016/j.ophtha.2023.08.001
Question
What are the characteristics of hearing dysfunction in patients receiving teprotumumab?
Background/Summary of Findings
There have been numerous reports of audiological dysfunction associated with teprotumumab. However, no large studies evaluating hearing symptoms and audiometry testing before, during, and after teprotumumab treatment have been previously performed. This was a case series from a single academic site that included patients receiving teprotumumab infusions who consented to pre-, mid-, and posttreatment audiometric testing by certified clinical audiologists. Decibel hearing threshold was measured at 250 Hz, 500 Hz, 1 kHz, 4 kHz, and 8 kHz pure tone frequencies for all ears tested, and each ear was tracked separately for analysis. Patients were grouped into either “baseline normal hearing” or “baseline hearing loss.”
A total of 44 ears of 22 patients (19 women, 3 men; mean age 52.4 years) were analyzed, with 16 having normal baseline hearing and 28 having baseline hearing loss; 38.6% of all ears had posttreatment hearing loss that met ototoxicity criteria. Notably, 4 of the 16 ears initially having baseline normal status had posttreatment hearing loss consistent with ototoxicity.
The authors concluded that teprotumumab influences hearing function, especially at higher frequencies (affects ability to understand speech in noisy environments) and in older patients, and that audiometric testing is critical to inform educating patients on possible teprotumumab treatment.
Clinical Value/Implications
This study is an important reminder of the necessity of considering how medication side effects need to be addressed with patients prior to initiating treatment of any kind. In this particular study, the quality-of-life benefits achieved with the use of teprotumumab could be offset by loss of hearing functionality in those vulnerable. Predicting those who are and are not susceptible to ototoxicity should be considered in patients with thyroid eye disease eligible for teprotumumab.
Study of Late-Onset Stargardt Type I Disease: Characteristics, Genetics and Progression
Li CHZ, Pas JAAH, Corradi Z, et al. Study of Late-Onset Stargardt Type 1 Disease: Characteristics, Genetics, and Progression. Ophthalmology. 2024;131(1):87-97. doi:10.1016/j.ophtha.2023.08.011
Question
What are the characteristics, underlying genetics, and disease progression of patients with late-onset Stargardt disease, and how do these characteristics differ from geographic atrophy?
Background/ Summary of Findings
Stargardt disease has a wide range of phenotypes and, although originally considered to be juvenile in its onset, can occur later in life. Late-onset Stargardt has been shown to be increasing in proportion in newly diagnosed Stargardt disease cases and shares some phenotypic features consistent with age-related macular degeneration. In one study, 22% of patients with Stargardt disease were previously misdiagnosed as age-related macular degeneration, which had the potential to lead to mistreatment.
The median age of onset was 55, and the median age of diagnosis was 59 years of age. In total, 89% of patients were initially symptomatic with self-reported decrease in visual acuity being the predominant symptom;98.9% of eyes showed posterior pole and macular flecks on the initial fundus autofluorescence imaging, 33% had foveal sparing with encircling atrophy ≥180°, 21% had atrophy with foveal involvement, 39% had extrafoveal atrophy, and 7% of eyes had no atrophy on initial presentation.
A combination of mild and severe ABCA4 variants was the most common genotype, and there were no cases including two severe variants.
From a disease progression standpoint, the median time from onset to visual impairment was 9.0 years for mild, 12.0 for moderate, and 15.0 years for severe impairment. Median atrophy growth was 0.590 mm2/year for definitely decreased autofluorescence and 0.650 mm2/year for total decreased autofluorescence.
Clinical Value/Implications
Having an understanding of the general presentation of late-onset Stargardt disease and how its unique pattern of atrophy progresses will help the practitioner correctly identify this condition, avoid misdiagnosis as age-related macular degeneration, and subsequently guide appropriate management in order to maximize quality of life for patients with late-onset Stargardt disease.
Risk of Noninfectious Uveitis After Coronavirus Disease 2019 Vaccination in a United States Claims Database
Kumar A, Miller DC, Sun Y, Arnold BF, Acharya NR. Risk of Noninfectious Uveitis after Coronavirus Disease 2019 Vaccination in a United States Claims Database. Ophthalmology. 2023;130(12):1269-1278. doi:10.1016/j.ophtha.2023.07.017
Question
Is there a risk of noninfectious uveitis following COVID-19 vaccination in patients not previously having a history of uveitis?
Background/Summary of Findings
Throughout the SARS-CoV-2 pandemic, there have been multiple case reports published on the uncommon occurrence of noninfectious uveitis after recent administration of BNT162b2, CHAdOx1 nCoV-19, mRNA-1273, and Ad26.COV2 vaccines. It has been proposed that an exaggerated immune response after vaccination is responsible for unilateral or bilateral anterior, posterior, or pan-uveitis occurring soon after administration.
This was a retrospective matched cohort study and self-controlled case series analysis of the rates of noninfectious uveitis identified with International Classification of Disease, Tenth Revision codes using a longitudinal, real-world data asset with deidentified administrative claims and electronic health record data (Optum labs data warehouse) from December 11, 2020, through November 30, 2021. Included were 2,305,689 chronically insured patients with Medicare advantage or commercial insurance who received a COVID-19 vaccination during the study period and a matched historical group of 2,305,689 unvaccinated patients. In the self-controlled case series design, 686 patients from the vaccinated cohort who had a noninfectious uveitis event during the study period were included. Patients with prior uveitis histories were excluded.
Hazard ratios for noninfectious uveitis were calculated using Cox proportional hazards models in the matched cohort design. Incidence rate ratios comparing noninfectious uveitis incidence in exposed postvaccine risk periods and unexposed control periods within an individual were calculated using conditional Poisson regression models in the self-controlled case series design. Models were adjusted for age, recent receipt of non–COVID-19 vaccinations, corticosteroid or immunosuppressive use, and smoking history. Subgroup analyses were conducted by vaccination type and age group.
The adjusted hazard ratio comparing noninfectious uveitis incidence in the vaccinated to the unvaccinated was 0.91, showing that there was not an overall increased risk of noninfectious uveitis after vaccination and, in fact, were consistent with the reported crude incidence rates of noninfectious uveitis in the United States. There was, however, an increased risk ratio of 1.40 in the youngest subgroup (ages 5-44) that the authors suggest could be due to a heightened immune response in younger patients. They noted that this increased risk would warrant further research before being able to generalize these findings.
Clinical value/implications
This cohort study supports that the overall risk of developing noninfectious uveitis in patients not previously having a uveitis diagnosis is unlikely to be heightened by receiving COVID-19 vaccination. Broadly speaking, these results further the public health implications of COVID-19 vaccination and the eyes. For practitioners, these results provide additional educational points to discuss with our patients if the subject is broached.
Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study
Park JG, Adrean SD, Begaj T, et al. Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study. Ophthalmology. 2024;131(1):66-77. doi:10.1016/j.ophtha.2023.08.025
Questions
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Is surgical repair a viable option in macular telangiectasia–associated full-thickness macular holes?
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What types of surgery are used in patients undergoing repair of macular telangiectasia–associated full-thickness macular holes?
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What is the success rate of those interventions?
Background/Summary of Findings
Although full-thickness macular hole development in macular telangiectasia type 2 is a rare event, there is no consensus on whether surgical repair is a viable option in these cases and, if so, which surgical strategies are beneficial. Although multiple surgical techniques have been reported in the literature in various case series, no comparison of their various outcomes has been explored.
In this retrospective study, surgeons from around the world were invited to submit consecutive cases of macular telangiectasia–associated full-thickness macular holes. Pre- and postoperative images submitted were reviewed by two trained graders. The primary outcome was anatomic closure of the macular telangiectasia–associated full-thickness macular hole. Secondary outcomes were numerous and included best pre- and postoperative visual acuities.
A total of 63 surgeries from 30 surgeons worldwide were included. The mean age of patients was 68.1 years with a 60% female/40% male distribution. Of the 63 procedures, there were 34 vitrectomies with internal limiting membrane peel, 22 internal limiting membrane flaps, 5 autologous retinal transplantations, 1 retinotomy, and 1 subretinal bleb performed.
Successful closure rates were 47% for internal limiting membrane peel, 90% for internal limiting flaps, and 100% for autologous retinal transplantations. The solitary case employing nasal retinotomy was successful, and the case using a subretinal bleb was unsuccessful. Mean postoperative best-corrected visual acuities were 20/110 with internal limiting membrane peels, 20/144 with internal limiting membrane flaps, and 20/200 with autologous retinal transplantations. Almost all patients achieving successful anatomic closure had improvement in their scotomas, and this was consistent across all techniques that were successful.
Overall, surgical closure resulted in improved best-corrected visual acuity in 57% of macular telangiectasia–associated full-thickness macular holes, with internal limiting membrane flaps achieving better anatomical and functional outcomes than internal limiting membrane peel alone. The authors noted that autologous retinal transplantations may be a viable option, but their sample was too small to achieve significance. They noted that the study’s limitations were its retrospective nature, the lack of standardization with the choice of surgical intervention, different surgical techniques, and inability to determine whether the timing of surgery relative to the timing of the advanced disease state would influence outcomes.
Clinical Value/Implications
Although macular telangiectasia–associated full-thickness macular holes are rare, it is important to recognize that surgical options exist that provide patients the potential for improved vision and reduced scotoma size. When encountering patients with advanced macular telangiectasia type II, surgical referral should be considered.
Immediate Sequential Bilateral Surgery in Refractive Lens Exchange Patients: Clinical Outcomes and Adverse Events
Hannan SJ, Schallhorn SC, Venter JA, Teenan D, Schallhorn JM. Immediate Sequential Bilateral Surgery in Refractive Lens Exchange Patients: Clinical Outcomes and Adverse Events. Ophthalmology. 2023;130(9):924-936. doi:10.1016/j.ophtha.2023.04.013
Question
Can immediate sequential bilateral refractive lens exchange surgery achieve equivalent safety and visual outcomes as a traditional delayed sequential approach?
Background/Summary of Findings
The standard of care for the timing of eyes going through cataract surgery is a delay in surgery from one eye to the next (delayed sequential bilateral surgery). Staggering a patient’s two eyes provides theoretical benefits in refining refractive outcomes of the patient’s second eye as well as reducing the potential of bilateral vision-limiting problems as the patient recovers. Performing surgery on the patient’s two eyes immediately, one following the other, known as immediate sequential bilateral surgery, offers its own advantages: less time in both clinic and surgery (which offers cost and convenience savings to the patient, insurance panels, and surgery centers), a quicker return to function, and eliminating the period of surgically induced anisometropia often experienced in patients receiving delayed sequential bilateral cataract surgery. A refractive lens exchange is essentially cataract surgery prior to the development of visually significant cataracts performed for its refractive benefit. These patients offer a useful surrogate to patients with cataracts in investigating the utility of immediate sequential bilateral surgery, as the clear or semiclear crystalline lens is easier to remove and therefore has a lower rate of complications, and the patients undergoing refractive lens exchange are often younger and have need to return to function more quickly. This is a large multicenter (United Kingdom-based centers) review of 33,660 eyes undergoing immediate sequential bilateral refractive lens exchange. Refractive outcomes and complications were monitored.
Refractive outcomes were excellent, with ~85% of patients being within 0.5 D of their predicted outcome. Fifty-five intraoperative eyes suffered intraoperative adverse events—although this number is slightly skewed as any patient developing an intraoperative adverse event on their first eye was immediately disqualified from the study as their second eye surgery was canceled and they were treated in a delayed sequential bilateral surgery fashion. Of the 55 studied eyes, 11 required further surgery as a result of their adverse event. Two hundred sixty-seven eyes developed an adverse event within the first postoperative month, which was most commonly cystoid macular edema (n = 172). Corneal edema lasting beyond the first postoperative month was encountered in 28 eyes. All but two resolved by 3 months postoperatively with one requiring a corneal transplant. Bilateral persistent inflammation was rare, occurring in only 18 eyes, with all but three resolving by 3 months. Persistent increased intraocular pressure occurred in 27 eyes, and all resolved by 3 months, except one case associated with herpetic eye disease. There were no cases of infectious endophthalmitis and a single retinal detachment affecting one eye in the cohort.
Clinical Value/Implications
In this review of immediate sequential bilateral surgery for patients undergoing refractive lens exchange, all refractive outcomes and adverse events were in line with, or superior to, existing published data of delayed sequential bilateral surgery. Given the many practical advantages of immediate sequential bilateral surgery, this study in a refractive lens exchange population supports consideration for a move toward immediate sequential bilateral cataract surgery, at least as an option for patients in the future. Given third-party payer regulations/limitations in United States, it is most practical to provide this option in a refractive lens exchange population.