Current Issue

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In this week’s issue

• Intravitreal topotecan is effective against refractory or recurrent vitreous seeds with morphology corresponding to the number of injections needed.
• A cohort study from California showed decreasing or steady trends in disparities in ROP incidence between 2012 to 2021, contrasting national trends.
• Changes in vessel density of the retinal vasculature appear to manifest in the preclinical phase of Alzheimer’s disease and may serve as a disease biomarker.

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Ophthalmology

Intravitreal topotecan for vitreous seeds in retinoblastoma

Got seeds? Topotecan can weed them out! Retinoblastoma, a highly curable childhood cancer, has seen significant advances in treatment, with intravenous and intra-arterial chemotherapy revolutionizing eye salvage, particularly in managing vitreous seeds. Intravitreal chemotherapy, especially using melphalan and topotecan, has improved outcomes for refractory or recurrent vitreous seeds, though ocular complications and the need for frequent injections remain challenges. This retrospective, non-comparative study analyzed 91 eyes of 90 retinoblastoma patients treated between 2013 and 2019, focusing on vitreous seed regression, eye salvage, and risk factors for recurrence after intravitreal topotecan injections, with additional interventions including chemotherapy, cryotherapy, and brachytherapy as needed. In this study of 90 retinoblastoma patients (median age 18 months), vitreous seeds regressed in 97% of eyes after intravitreal topotecan injections, with a median of 3 injections required (P = 0.007 for refractory cases in eyes with cloud-type seeds). Vitreous seeds recurred in 19% of eyes, with recurrence associated with older age (P = 0.018) and retinal tumor recurrence (P < 0.01), while 15% of eyes ultimately required enucleation. Intravitreal chemotherapy, particularly with melphalan and topotecan, has demonstrated high efficacy in treating refractory and recurrent vitreous seeds in retinoblastoma, achieving significant eye salvage rates with minimal toxicity and improved visual outcomes, though treatment response varies based on the morphologic characteristics of the seeds.

JAMA Ophthalmology  

Trends in retinopathy of prematurity from 2012 to 2021 in California

Different race, different case? Retinopathy of prematurity (ROP) and associated racial disparities have been increasing in prevalence within the US since 2003. A study included a cohort of premature infants prior to 32 weeks of age across California from 2012 to 2021. Factors included clinical and sociodemographic covariates of the population with and without ROP, trends in screening, and incidence of ROP in total by race and ethnicity with a primary endpoint of ROP incidence. Results showed that among all very preterm infants (<32 weeks gestational age), the incidence of ROP decreased from 31% in 2012 to 29% in 2021 in California. Incidence rates of ROP among Asian and Hispanic individuals decreased most quickly compared to other racial and ethnic groups. The decreased ROP incidence over time and among specific ethnic groups in California warrants further research regarding potential causes for the contrast between what is observed in California compared to increasing national trends. 

IOVS

Can OCTA measurements detect preclinical Alzheimer’s? 

Seeing Alzheimer's one vein at a time. Using the eye to detect Alzheimer’s Disease (AD) has become a popular field of study because methods can be employed that are quick, noninvasive, and lower cost than current methods to identify amyloid beta. Previous studies have shown that vessel density may be increased in patients with mild cognitive impairment and AD, but there is less data on changes over time. This cohort study examined the potential use of biomarkers identified by OCTA to detect AD in the preclinical phase (pAD). 148 participants were followed for two years and assigned to three groups based on amyloid beta status established by PET scan: those who were negative at baseline and follow-up (Aβ–), those who converted from negative to positive (Aβ–+), and those who were positive at both timepoints (Aβ++). The endpoints measured were vessel density (VD) of the optic nerve head (ONH) and inner and outer rings of the macula, and changes in the foveal avascular zone (FAZ).  While there were increases in VD across all groups, the increases were only statistically significant in the (Aβ–) group in the ONH and macular rings. Additionally, there were significantly higher vessel density values in the Aβ++ group compared to the Aβ– group in the inner and outer rings of the macula. There were no significant changes over time in the FAZ in any group. This study supports changes to VD over time, particularly in Aβ– patients. Longer longitudinal studies may provide insight into the development of these changes and their clinical correlation. 

Cornea

Lotilaner ophthalmic solution, 0.25%, for Demodex blepharitis

No need to BUG out over these drops! Demodex blepharitis is one of the most common reasons individuals seek eye care in the United States. It consists of itching, foreign body sensation, eyelid inflammation, and collarettes at the base of the eye lashes. Lotilaner ophthalmic solution, 0.25%, is a newer treatment option used to get rid of the Demodex mites that reside at the base of the eyelashes. The purpose of this study is to evaluate the long-term safety and efficacy of lotilaner ophthalmic solution, 0.25%. Across the 11 clinical sites in the study, 239 patients qualified for participation. Participants were evaluated at 180 days and 365 days after the initiation of the original 6-week treatment with lotilaner ophthalmic solution, 0.25% or the placebo. One adverse effect, blurry vision, occurred in the study group (0.8%). The study group showed less collarettes and less erythema on the upper eyelid border at every assessment up to 1 year after initiation of treatment. These results show that the effects of the Lotilaner ophthalmic solution, 0.25%, can last well beyond completion of therapy. 

Trans Vis Sci Technol

Automatic determination of endothelial cell density from donor cornea images

Why count cells manually when deep learning can see you through? Measuring corneal endothelial cell density (ECD) is a critical step of evaluating donor corneal health for keratoplasty procedures and is usually done manually via specular microscopy. However, the quality of corneal ECD analysis varies; institutions with image reading centers that employ full-time staff tend to acquire more accurate measurements and are therefore capable of obtaining a better sense of donor tissue quality. To date, a fully automated corneal endothelial image analysis system does not exist. In this multi-site validation study, researchers trained and validated a deep learning model to perform automatic corneal endothelial cell segmentation and inference of ECD from 15,312 donor images. This model was then validated against manual corneal ECD counts on 1939 higher-quality corneal endothelial images. Corneal ECD measurements from both methods were in excellent agreement, with rc of 0.77 (P < 0.001), bias of 123 cells/mm2 (P < 0.001), and 81% of the automated corneal ECD values within 10% of the manually-obtained corneal ECD values. In the linear regression models predicting differences in corneal ECD between manual and automated methods, only donor age was statistically but not clinically significant. This study demonstrates the ability of deep learning to aid in the acquisition of corneal ECD counts from donor images at an equivalent level of accuracy compared to manual counts obtained by trained staff, with a significantly reduced analysis time.

United Kingdom Prospective Diabetes Study (UKPDS)

This UKPDS sought to answer a variety of questions related to the natural history and impact of hyperglycemia control for patients with Type II Diabetes. Such questions included what risk factors dictate the incidence and progression of diabetic retinopathy, in addition to what impact intensive glycemic control would yield on incidence and progression.

Key Points:

• Risk factors for development and progression of diabetic retinopathy were noted to be higher blood glucose levels, high blood pressure, and interestingly, not smoking
• The intensive glycemic control group had a lower A1c at study endpoints than the conventional diet-control group (7.0% versus 7.9%)
• The intensive glycemic control group had lower likelihood of development of microvascular complications (need for PRP), but did have elevated risk of hypoglycemia

Overall, the UKPDS is a landmark study because it highlighted the important risk factors of high blood pressure and hyperglycemia in promoting the onset or progression of retinopathy in patients with Type II (non-insulin-dependent) diabetes mellitus. Furthermore, along with the DCCT (which studied Type I Diabetics), these studies helped to identify a new target for blood glucose control in Diabetic patients.

A 68-year-old woman with a history of invasive ductal carcinoma treated with lumpectomy, chemotherapy, and radiation therapy presents for a routine ophthalmic examination. She complains of mildly blurred vision but is not bothered by these symptoms. She is currently on tamoxifen, trastuzumab, letrozole, and anastrozole as part of her adjuvant therapy. During fundus examination, yellow-white refractile deposits are noted in the macula of both eyes and an OCT is subsequently performed. Fundus photos and OCT are depicted below. 

Which of the patient's therapies are most likely responsible for the retinal findings depicted?

A. Tamoxifen

B. Trastuzumab

C. Letrozole

D. Anastrozole

E. Radiation 

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