Retina News December 2022

Comparison in Retreatments between Bevacizumab and Ranibizumab Intravitreal Injections for Retinopathy of Prematurity- A Multicenter Study

Purpose: To compare the types and dosages of anti-VEGFs to ascertain whether specific dosages or types of injection were associated with retreatment in clinical practice in the US.

Design: Multicenter, retrospective, consecutive series.

Subjects: Patients with ROP treated with anti-VEGF injections from 2007 to 2021.

Methods: Sixteen sites from the US participated. Data collected included demographics, birth characteristics, examination findings, type and dose of anti-VEGF treatment, retreatment rates, and time to retreatment. Comparisons of retreatment rates between bevacizumab and ranibizumab intravitreal injections were made.

Main outcome measures: Relative rate of retreatment between varying types of anti-VEGF therapy, including bevacizumab and ranibizumab, and the various dosages used for each.


Data from 873 eyes of 661 patients (61% males and 39% females) were collected. After exclusion of 40 eyes treated with laser prior to anti-VEGF injection and 266 eyes retreated with laser at or beyond 8 weeks after the initial anti-VEGF treatment, 567 eyes of 307 patients (63% males and 37% females) remained and were included in the primary analysis. There was no difference between the no-retreatment and retreatment groups in terms of birthweight, gestational age, age at first injection, ROP stages, or number of involved clock hours.

The retreatment group had a larger percentage of A-ROP (34 vs 18%, P < .001), and greater percentage of Zone 1 ROP (49 vs 34%, P = .001) than the no retreatment group.

Ranibizumab use was associated with a higher rate of retreatment than bevacizumab use (58% vs 37%, P < .001), while the rate of retreatment was not associated with a specific dose of ranibizumab (R2 = .67, P = .32).

Meanwhile, lower doses of bevacizumab were associated with higher rates of retreatment compared to the higher doses (R2 = .84, P = .01). There was a dose specific trend with higher doses trending towards lower retreatments for bevacizumab.

Conclusions: In a multicenter study of ROP patients initially treated with anti-VEGF therapy, ranibizumab and lower dose bevacizumab use were associated with an increased rate of retreatment when compared to higher dose bevacizumab.

Randomized Trial to Evaluate the Efficacy of the Nanodropper Device for Pupillary Dilation and Cycloplegia in Children

Purpose: We evaluated the noninferiority of 10.4 μl of eye drops eluted with a commercially available eye drop adapter, the Nanodropper (Nanodropper, Inc), on pupillary dilation and cycloplegia in children compared with the standard of care (SOC), 50 μl of eye drops.

Design: Prospective randomized trial.

Participants: Pediatric patients scheduled for routine pupillary dilation at the University of California, San Francisco, at the Pediatric Ophthalmology Clinic were enrolled. Each participant provided 1 eye for the intervention group (Nanodropper) and 1 eye for the control group (SOC).

Methods: Participants were randomized to receive small-volume dilating drops in 1 eye (Nanodropper) and SOC dilating drops in the other eye. Dilation was performed using 1 drop each of 1% cyclopentolate, 1% tropicamide, and 2.5% phenylephrine. Refraction and pupillometry were obtained before and 30 minutes after dilation. A noninferiority analysis was performed to assess change from before to after dilation in spherical equivalent and in pupil constriction percentage and maximum pupil diameter after dilation.

Main outcome measures: Spherical equivalent, maximum pupil diameter, and pupil constriction percentage.

Results: One hundred eyes of 50 patients were included, with a mean ± standard deviation age of 9 ± 3 years. After controlling for baseline measurements, the spherical equivalent after dilation was 0.05 diopter (D) more (95% confidence interval [CI], -0.28 to 0.37 D) in the Nanodropper arm, which did not achieve noninferiority. Maximum pupil diameter after dilation was lower in the Nanodropper group (mean, -0.01 mm; 95% CI, -0.20 to -0.03), which did achieve noninferiority. Constriction percentage after dilation was 0.57 percentage points more (95% CI, -1.38 to 2.51 percentage points) in the Nanodropper group, which did not achieve noninferiority.

Conclusions: Administration of eye drops using a small-volume adaptor demonstrated similar efficacy to SOC in a pediatric population. Strict noninferiority was met only for pupillary dilation and not for cycloplegia or constriction percentage; however, the small differences in the effect of the Nanodropper versus SOC on all primary outcomes were not clinically significant. We conclude that small-volume eye drops have the potential to decrease unnecessary medical waste and medication toxicity while maintaining therapeutic effect.

Benign Lobular Inner Nuclear Layer Proliferations of the Retina Associated with Congenital Hypertrophy of the Retinal Pigment Epithelium

Purpose: To report the clinical and imaging findings of 4 patients with benign intraretinal tumors, 2 of which were associated with retinal pigment epithelium (RPE) hypertrophy. To our knowledge, this condition has not been described previously and should be distinguished from retinoblastoma and other malignant retinal neoplasms.

Design: Retrospective case series.

Participants: Four patients from 3 institutions.

Methods: Four patients with intraretinal tumors of the inner nuclear layer (INL) underwent a combination of ophthalmic examination, fundus photography, fluorescein angiography, OCT, OCT angiography, and whole exome sequencing.

Main outcome measures: Description of multimodal imaging findings and systemic findings from 4 patients with benign intraretinal tumors and whole exome studies from 3 patients.

Results: Six eyes of 4 patients 5, 13, 32, and 27 years of age were found to have white intraretinal tumors that remained stable over the follow-up period (range, 9 months-4 years). The tumors were unilateral in 2 patients and bilateral in 2 patients. The tumors were white, centered on the posterior pole, and multifocal, with some consisting of multiple lobules with arching extensions that extended beyond the central tumor mass. OCT demonstrated these lesions to be centered within the INL at the border of the inner plexiform layer. In addition, 2 patients demonstrated congenital hypertrophy of the RPE (CHRPE) lesions. Three of 4 patients underwent whole exome sequencing of the blood that revealed no candidate variants that plausibly could account for the phenotype.

Conclusions: We characterize a novel benign tumor of the INL that, in 2 patients, was associated with separate CHRPE lesions. We propose the term benign lobular inner nuclear layer proliferation to describe these lesions.

Intraocular Lens Calcification After Pseudophakic Endothelial Keratoplasty

Benjamin Memmi et al. Am J Ophthalmol.Free article

Purpose: To determine the incidence and to document risk factors for intraocular lens (IOL) calcification after pseudophakic endothelial keratoplasty.

Methods: We retrospectively studied 2700 consecutive penetrating, anterior lamellar and endothelial keratoplasties carried out between December 1992 and June 2022 at the National Eye Hospital, Paris, France.

Design: Retrospective cohort study.

Results: All IOL calcification cases were associated with endothelial keratoplasty. Out of 588 endothelial keratoplasty procedures, 576 eyes were pseudophakic at the end of surgery. Fourteen cases of IOL calcification were observed during follow-up. The cumulative incidence of IOL calcification after endothelial keratoplasty was 4.5%±1.3% at 60 months. Hydrophilic acrylic IOL material (P < .001) and use of SF6for anterior chamber tamponade (P = .001) were significantly and independently associated with the cumulative incidence of IOL calcification.

Conclusion: The incidence of IOL calcifications seems to be around 5%. Ophthalmologists should avoid hydrophilic acrylic IOLs in patients with endothelial disorders. When the patient already has a hydrophilic IOL, SF6 should be avoided. The only effective treatment is IOL exchange.

In vivo longitudinal measurement of cone photoreceptor density in intermediate age-related macular degeneration

Xiaolin Wang et al. Am J Ophthalmol.

Purpose: To evaluate cone photoreceptor density in clinically unremarkable retinal regions in patients with age-related macular degeneration (AMD) using adaptive optics scanning laser ophthalmoscopy (AOSLO).

Design: Prospective case series with normal comparison group.

Methods: Ten eyes of seven patients with intermediate AMD were studied, including four with predominantly subretinal drusenoid deposits (SDD) and three without SDD. Macular regions with a clinical absence of AMD-associated lesions were identified by cone packing structure on AOSLO and optical coherence tomography. Cone density was measured in 1174 clinically unremarkable regions within the central subfield (CSF), the inner (IR), and outer rings (OR) of the Early Treatment Diabetic Retinopathy Study grid over 39.6 ± 3.3 months and compared with age-matched normal values obtained in 17 subjects.

Results: Cone density decreased at 98.3% of the examined locations over time in the eyes with AMD. In the CSF, IR, and OR, cones declined by -255 ± 135, -133 ± 45, and -59 ± 24 cones/degree2/year, respectively, in eyes with SDD, and by -212 ± 89, -83 ± 37, and -27 ± 18 cones/degree2/year, respectively, in eyes without SDD. The percentage of retinal loci with cone density lower than normal (Z-score < -2) increased over the follow-up: from 42% at the baseline to 80% at the last visit in eyes with SDD and from 31% to 70% in eyes without SDD.

Conclusions: AOSLO revealed cone photoreceptor loss in regions that appear otherwise unremarkable clinically. These findings may help explain the loss of mesopic sensitivity reported in these areas in eyes with intermediate AMD.

Choriocapillaris flow deficit as a biomarker for diabetic retinopathy and diabetic macular edema: 3-year longitudinal cohort: Choriocapillaris flow predicts DR progression and DME development

Purpose: To investigate the relationship between choriocapillaris flow deficit percentage (CC FD%) by swept-source optical coherence tomography angiography (SS-OCTA) and 3-year risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development.

Design: Prospective, observational cohort study.

Methods: A total of 903 participants with type 2 diabetes mellitus (T2DM) without DR or with mild non-proliferative DR (NPDR) free of DME at baseline were followed up annually for 3 years. All participants underwent standard 7-field fundus photography and spectral-domain OCT. SS-OCTA was used for retinal and choriocapillaris imaging and 3 × 3 mm2 macular CC FD% was quantified. Univariate and multivariate logistic models were used to evaluate the association between CC FD% and two or more steps of DR progression and DME development. The additional predictive value of CC FD% for outcome events was assessed using C-statistic, net reclassification index (NRI), and integrated discrimination improvement index (IDI).

Results: Over 3 years, 295 of 1805 eyes (16.34%) developed DR progression, and 118 eyes (6.54%) developed DME. A higher average CC FD% was correlated with DR progression (odds ratio [OR], 3.41 per SD increase, 95% confidence interval [CI]: 2.65-4.39, P<0.001) and DME development (OR, 1.37 per SD increase, 95% CI: 1.06-1.77, P=0.016) after adjusting for confounders. In the ETDRS regions, increased CC FD% in all fields was associated with DR progression; however, increased CC FD% in the inferior field was associated with DME development. Compared with the models based on established risk factors, the addition of average CC FD% significantly improved the C-statistics for DR progression (0.712 to 0.777, P<0.001) and DME occurrence (0.743 to 0.773, P=0.044). The estimated NRIs and IDIs (all >0) indicated that the addition of CC FD% led to a significant improvement in the discriminative performance for endpoints.

Conclusion: CC FD% is independently associated with DR progression and DME development in the Chinese T2DM population and provides incremental predictive value beyond traditional risk factors and retinal microvascular parameters. Further inclusion of CC FD% in DR prediction models helps guide population-based screening and personalized management.

Keywords: SS-OCTA; choriocapillaris; cohort; diabetic retinopathy; prediction model.