Publications by authors named "Natalia F Callaway"

43 Publications

Visual acuity and progression of macular atrophy in patients receiving intravitreal anti-VEGF for age-related macular degeneration.

Eur J Ophthalmol 2021 Mar 29:11206721211001708. Epub 2021 Mar 29.

Byers Eye Institute, Horngren Family Vitreoretinal Center, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Purpose: Whether intravitreal anti-vascular endothelial growth factors (VEGFs) cause retinal atrophy is still a subject of debate. We reported 13 eyes that received several injections of anti-VEGF for wet age-related macular degeneration (AMD) with good visual acuity despite geographic atrophy on imaging.

Methods: This is a case series study conducted at Byers Eye Institute at Stanford University. Patients of three retina specialists with wet AMD who received six or more intravitreal injection of anti-VEGFs with visual acuity of 20/60 or better and incomplete RPE and outer retina atrophy (iRORA) or complete RPE and outer retinal atrophy (cRORA) were enrolled in this case series. Different imaging modalities were reviewed by three retina specialists comparing the baseline with the most recent exam.

Results: About 13 eyes of 10 patients met the selection criteria. Eleven eyes were classified as iRORA and 2 as cRORA. Despite the development of macular atrophy on imaging after an average of 38.1 injections, eyes maintained stable visual acuity.

Conclusion: The discrepancy between structural and functional findings in this cohort suggests that patients treated by anti-VEGF drugs exhibit divergent clinical outcomes for currently unknown reasons. The authors propose anti-VEGF may affect melanosomes within RPE without disrupting RPE and photoreceptors function completely. This requires further investigation.
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http://dx.doi.org/10.1177/11206721211001708DOI Listing
March 2021

Key factors in a rigorous longitudinal image-based assessment of retinopathy of prematurity.

Sci Rep 2021 Mar 8;11(1):5369. Epub 2021 Mar 8.

Department of Ophthalmology, Byers Eye Institute, Stanford School of Medicine, 2452 Watson Court, Palo Alto, CA, 94303, USA.

To describe a database of longitudinally graded telemedicine retinal images to be used as a comparator for future studies assessing grader recall bias and ability to detect typical progression (e.g. International Classification of Retinopathy of Prematurity (ICROP) stages) as well as incremental changes in retinopathy of prematurity (ROP). Cohort comprised of retinal images from 84 eyes of 42 patients who were sequentially screened for ROP over 6 consecutive weeks in a telemedicine program and then followed to vascular maturation or treatment, and then disease stabilization. De-identified retinal images across the 6 weekly exams (2520 total images) were graded by an ROP expert based on whether ROP had improved, worsened, or stayed the same compared to the prior week's images, corresponding to an overall clinical "gestalt" score. Subsequently, we examined which parameters might have influenced the examiner's ability to detect longitudinal change; images were graded by the same ROP expert by image view (central, inferior, nasal, superior, temporal) and by retinal components (vascular tortuosity, vascular dilation, stage, hemorrhage, vessel growth), again determining if each particular retinal component or ROP in each image view had improved, worsened, or stayed the same compared to the prior week's images. Agreement between gestalt scores and view, component, and component by view scores was assessed using percent agreement, absolute agreement, and Cohen's weighted kappa statistic to determine if any of the hypothesized image features correlated with the ability to predict ROP disease trajectory in patients. The central view showed substantial agreement with gestalt scores (κ = 0.63), with moderate agreement in the remaining views. Of retinal components, vascular tortuosity showed the most overall agreement with gestalt (κ = 0.42-0.61), with only slight to fair agreement for all other components. This is a well-defined ROP database graded by one expert in a real-world setting in a masked fashion that correlated with the actual (remote in time) exams and known outcomes. This provides a foundation for subsequent study of telemedicine's ability to longitudinally assess ROP disease trajectory, as well as for potential artificial intelligence approaches to retinal image grading, in order to expand patient access to timely, accurate ROP screening.
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http://dx.doi.org/10.1038/s41598-021-84723-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940603PMC
March 2021

Higher prevalence of fundus haemorrhages in early-screened (NEST Study) as compared to late-screened (SUNDROP Study) newborn populations.

Br J Ophthalmol 2021 Jan 29. Epub 2021 Jan 29.

Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, USA

Background/aims: To determine whether timing of ophthalmic screening influences prevalence of neonatal fundus haemorrhages. We compared the prevalence of fundus haemorrhages in two populations: term newborns screened early (less than 72 hours) and preterm newborns screened late (4-11 weeks). Additionally, we reviewed the literature on timing and prevalence of newborn haemorrhages.

Methods: Retrospective observational cohort study. Infants who underwent wide-angle ophthalmic digital imaging over one overlapping year in the Newborn Eye Screen Testing (NEST) or Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) programme were included. The PubMed database was filtered to include English-language articles dating back to 1950. Nine articles were selected for review based on inclusion of the prevalence of newborn fundus haemorrhages at multiple time points.

Results: A total of 202 patients received early imaging in the NEST cohort and 73 patients received late imaging in the SUNDROP cohort. In the NEST cohort, 20.2% of newborns had haemorrhages. In contrast, we found haemorrhages in only one case or 1.4% of the SUNDROP cohort. Using prevalence data from nine additional studies, we developed a predicted probabilities model of newborn haemorrhages. Per this model, the probability of seeing a haemorrhage if you screen an infant at 1 hour is 18.8%, at 2 weeks is 2.9% and at 1 month is 0.28%.

Conclusion: We found a significant difference in the prevalence of fundus haemorrhages between the early-screened NEST cohort and the late-screened, preterm SUNDROP cohort. Likely, this difference is due to the transient nature of most newborn haemorrhages.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317908DOI Listing
January 2021

Risk of Retinal Artery Occlusion in Patients with Migraine.

Am J Ophthalmol 2020 Dec 24;225:157-165. Epub 2020 Dec 24.

Department of Ophthalmology, Byers Eye Institute, Horngren Family Vitreoretinal Center, Stanford University School of Medicine, Palo Alto, California, USA. Electronic address:

Purpose: We sought to determine if migraine is associated with increased risk of retinal artery occlusion (RAO).

Design: Retrospective cohort study.

Methods: We reviewed a large insurance claims database for patients with migraine and matched control subjects without migraine between 2007 and 2016. Cox proportional hazard regression models were used to investigate the association between migraine and risk of all RAO, central RAO (CRAO), branch RAO (BRAO), and "other" RAO, which includes transient and partial RAO. Primary outcome measures included the incidence of all RAO, including CRAO, BRAO, and other RAO, after first migraine diagnosis.

Result: There were 418,965 patients with migraine who met the study criteria and were included in the analysis with the appropriate matched control subjects. Among the 418,965 patients with migraine, 1060 (0.25%) were subsequently diagnosed with RAO, whereas only 335 (0.08%) of the patients without migraine were diagnosed with RAO. The hazard ratio (HR) for incident all RAO in patients with migraine compared with those without migraine was 3.48 (95% confidence interval [CI] 3.07-3.94; P < .0001). This association was consistent across all types of RAO, including CRAO (HR 1.62 [95% CI 1.15-2.28]; P = .004), BRAO (HR 2.09 [95% CI 1.60-2.72]; P < .001), and other types of RAO (HR 4.61 [95% CI 3.94-5.38]; P < .001). Patients with migraine with aura had a higher risk for incident RAO compared with those with migraine without aura (HR 1.58 [95% CI 1.40-1.79]; P < .001). This association was consistent for BRAO (HR 1.43 [95% CI 1.04-1.97]; P < .03) and other types of RAO (HR 1.67 [95% CI 1.45-1.91]; P < .001) but was not statistically significant for CRAO (HR 1.18 [95% CI 0.75-1.87]; P = .475). Significant risk factors for this association included increased age, male sex, acute coronary syndrome, valvular disease, carotid disease, hyperlipidemia, hypertension, retinal vasculitis or inflammation, and systemic lupus erythematosus.

Conclusions: Migraine is associated with increased risk of all types of RAO and migraine with aura is associated with increased risk of RAO compared with migraine without aura.
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http://dx.doi.org/10.1016/j.ajo.2020.11.004DOI Listing
December 2020

Intravitreal methotrexate and fluocinolone acetonide implantation for Vogt-Koyanagi-Harada uveitis.

Am J Ophthalmol Case Rep 2020 Sep 2;19:100859. Epub 2020 Aug 2.

Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

Purpose: To report a case of intravitreal methotrexate treatment and fluocinolone acetonide (Retisert®) implantation in a patient with Vogt-Koyanagi-Harada syndrome (VKH).

Observations: A 34-year-old male was referred for worsening vision and bilateral panuveitis consistent with VKH. He was treated with prednisone, mycophenolate mofetil, prednisolone acetate eye drops, and injections of triamcinolone and adalimumab. He failed to improve with these therapies and developed multiple adverse effects, including hepatotoxicity, severe eye pain, cataracts, and cystoid macular edema. We treated him with intravitreal methotrexate injections in both eyes, which rapidly improved his eye pain, inflammation, and vision. He subsequently underwent fluocinolone acetonide (Retisert®) implantation, cataract extraction with intraocular lens insertion, and Ahmed tube placement for long-term intraocular pressure control. His vision improved from hand motions to 20/30, intraocular pressure remained stable at 17, there was complete resolution of his panuveitis and uveitic macular edema, and his systemic medications were able to be discontinued.

Conclusions: /Importance: This case demonstrates intravitreal methotrexate may successfully treat intraocular inflammation, pain, and macular edema in VKH. Excellent long-term vision and reduction of adverse effects of systemic medications were also achieved with subsequent fluocinolone acetonide implantation. Combining these two targeted therapies may be an effective strategy in treating VKH in patients who have severe pain and cannot tolerate systemic therapy.
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http://dx.doi.org/10.1016/j.ajoc.2020.100859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415829PMC
September 2020

Conserved regression patterns of retinopathy of prematurity after intravitreal ranibizumab: A class effect.

Eur J Ophthalmol 2020 Jul 28:1120672120945101. Epub 2020 Jul 28.

Department of Ophthalmology, Fondazione Policlinico A. Gemelli, Catholic University of Sacred Heart, Rome, Italy.

Purpose: To determine if fluorescein angiographic (FA) findings after intravitreal ranibizumab (IVR) for retinopathy of prematurity (ROP) conform to a class effect previously described with bevacizumab.

Methods: Single-center retrospective case series of all infants treated with 0.2 mg (0.02 mL) IVR for Type 1 ROP from July 2016 to November 2018. FA were obtained at 40, 52, 62, and 72 weeks of postmenstrual age (PMA) using wide-angle photography. FA images were analyzed and the peripheral avascular areas measured with ImageJ using a reference disc diameter (DD). Based on the extent of the avascular area and tortuosity of the retinal vessels all eyes were classified into four categories: complete vascular maturity (vascularization within 2 DD of the ora serrata), VAA (avascular area >2 DD of the ora serrata), VAT (avascular area >2 DD of the ora serrata and posterior tortuosity), and reactivation (recurrence of stage disease).

Results: About 13 infants were enrolled and 24 eyes were available in this study. None of the eyes reached complete vascular maturity at an average PMA of 60 weeks, 7 (29%) eyes presented with VAA, 8 (33%) with VAT, and 9 (37.5%) reactivated. The reactivated eyes presented with the largest area of peripheral ischemia, followed by the VAT and then the VAA groups ( = 0.02).

Conclusion: IVR conforms to the previously described regression patterns following intravitreal bevacizumab for ROP indicative of a class effect. Follow-up using FA might help to optimize the management of these infants after injection of the drug.
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http://dx.doi.org/10.1177/1120672120945101DOI Listing
July 2020

Morning glory optic nerve in Aicardi syndrome: Report of a case with fluorescein angiography.

Eur J Ophthalmol 2020 Jul 16:1120672120942702. Epub 2020 Jul 16.

Department of Ophthalmology, Byers Eye Institute, Horngren Family Vitreoretinal Center, Stanford University School of Medicine Palo Alto, CA, USA.

Background: Aicardi syndrome is an X-linked condition that is associated with multiple ophthalmic malformations. Here, we report the first published fluorescein angiography (FA) study of a morning glory optic nerve in a patient with Aicardi syndrome and contralateral persistent fetal vasculature (PFV).

Case Description: A 12-day old full-term baby girl with a normal neurological exam was referred for evaluation of microphthalmia. The posterior segment of the right eye demonstrated chorioretinal lacunae typical of Aicardi syndrome and microphthalmos with a stalk consistent with PFV. The right eye imaging could not be captured due to the severe microphthalmos and cataract, however, fluorescein angioscopy was performed. The left eye demonstrated a morning glory appearing optic disc with peripapillary chorioretinal lacunae. Fluorescein angiography of the eye showed and late staining in the areas of ellipsoid chorioretinal lacunae emanating from the optic nerve and extensive peripapillary staining and late leakage of the optic nerve.

Conclusion: Patients with Aicardi syndrome can have morning glory optic nerve anomaly and PFV. Using FA under anesthesia to detect these abnormalities help in estimating the extend of the disease and its complications, which allows for better management of the complications.
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http://dx.doi.org/10.1177/1120672120942702DOI Listing
July 2020

Idiopathic bilateral inner retinal defects in a child.

Can J Ophthalmol 2020 Dec 6;55(6):e197-e199. Epub 2020 Jul 6.

Stanford University School of Medicine, Palo Alto, CA. Electronic address:

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http://dx.doi.org/10.1016/j.jcjo.2020.04.018DOI Listing
December 2020

Sex Differences in the Repair of Retinal Detachments in the United States.

Am J Ophthalmol 2020 11 5;219:284-294. Epub 2020 Jul 5.

Byers Eye Institute at the Stanford University School of Medicine, Palo Alto, California, USA.

Purpose: To investigate differences between women and men in the repair of rhegmatogenous retinal detachments (RRDs) in the United States.

Design: Retrospective cohort study.

Methods: Setting: A large insurance claims database.

Participants: Subjects with an incident RRD between 2007 and 2015.

Data: Demographic data, comorbid ocular conditions associated with RRD, systemic comorbidities, and surgical intervention (pneumatic retinopexy [PR], pars plana vitrectomy [PPV], laser barricade, or scleral buckle [SB]) were collected.

Main Outcome Measures: Odds of receipt of surgical intervention for incident RRD, time to repair, type of intervention, and the rate of reoperation by sex.

Results: The study period included 133 million eligible records with 61,071 cases of incident RRD among which 43% (n = 26,289) were women. The primary outcome model had 23,933 confirmed RRD cases with a 93% retinal detachment repair rate. Women had 34% reduced odds of receipt of surgical repair of an RRD (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.59, 0.73; P < .001) after adjusting for confounders. This effect persisted in all sensitivity models. Among patients who received repair, women were more often delayed (0.17 days, P = .04). Women were more likely to undergo primary laser barricade (relative risk ratio [RRR] 1.68, P < .001), primary SB (RRR 1.15, P < .001), and PR (RRR 1.07, P < .04) than men. The odds of reoperation were lower in women (OR 0.91, 95% CI 0.85, 0.96; P = .002) after adjustment.

Conclusions: Insured women are less likely than insured men to receive surgical intervention for an RRD. Based on the results of this study, if the odds of repair were equal between women and men in the United States, then 781 more women would receive surgery each year, or 7,029 more during the study period. Women are more likely to have the repair performed with scleral buckle, laser barricade, and pneumatic retinopexy. The reason for these sex differences in RRD repair remains unknown and requires further investigation.
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http://dx.doi.org/10.1016/j.ajo.2020.06.039DOI Listing
November 2020

Timing and Reoperation Rate of Rhegmatogenous Retinal Detachments Occurring During Major Ophthalmology Meetings.

Ophthalmic Surg Lasers Imaging Retina 2020 06;51(6):328-337

Background And Objective: To investigate whether surgical management of newly diagnosed rhegmatogenous retinal detachment (RRD) varies if patients are diagnosed during a major national ophthalmology conference.

Patients And Methods: This retrospective cohort study included 34,759 patients with incident RRD, of whom, 1,246 (3.6%) were diagnosed during dates of three national ophthalmology conferences, and 1,170 (3.4%) underwent surgery during conference dates. The authors identified patients with primary repair with cryotherapy, laser, scleral buckle, pneumatic retinopexy, or pars plana vitrectomy. Multinomial logistic regression models were used to determine patients' likelihood of receiving each type of repair within 30 days of their diagnosis depending on whether they were diagnosed during a national ophthalmology conference. Linear regression models were used to determine the relationship between the date patients were diagnosed and how long they waited to receive a repair. Main outcome measures included days between diagnosis with RRD and RRD repair, receiving repair on the same day of diagnosis, and reoperation rate within 30 days of the primary repair.

Results: Mean time from diagnosis to repair was 1.5 days (standard deviation: ± 2.4 days), and 71% of patients underwent repair within a day of diagnosis. Repairs were followed by a second surgery within 30 days in 11.1% of patients. Patients diagnosed during conferences waited 0.23 days longer between diagnosis and repair compared with patients diagnosed outside of conference dates (P = .001). Patients diagnosed with RRD during conferences were less likely to receive surgical repair within a day of diagnosis compared to patients diagnosed during non-conference dates (P = .037). Patients who were diagnosed with RRD during a conference date and also received surgery during a conference date were more likely to undergo a second surgery within 30 days of the primary procedure (P = .006) CONCLUSIONS: Patients diagnosed with RRD during national ophthalmology conference dates waited slightly longer for surgery, were slightly less likely to receive surgery within a day, and were more likely to undergo a second surgery within 30 days of the primary procedure. The "national meeting effect" phenomenon is present in ophthalmology, albeit to a lesser degree that is likely not visually significant. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:328-337.].
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http://dx.doi.org/10.3928/23258160-20200603-03DOI Listing
June 2020

Bilateral focal choroidal excavations in a patient with Stargardt disease and ocular toxoplasmosis.

Eur J Ophthalmol 2020 Jun 3:1120672120932092. Epub 2020 Jun 3.

Horngren Family Vitreoretinal Center, Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Introduction: Focal choroidal excavation (FCE) is a concavity of the choroid detected on optical coherence tomography (OCT). It is usually idiopathic and the affected eyes are otherwise healthy with near-normal overlying retinal architecture and good visual acuity.

Purpose: To report a case of bilateral conforming FCE in the setting of Stargardt disease and inactive ocular toxoplasmosis.

Case Report: A 20-year-old man with known history of Stargardt disease, healed toxoplasmosis, and high myopia presented to our ophthalmology department for follow-up examination and was found with bilateral FCEs not present in any of his previous examinations.

Conclusion: FCEs have been reported in the literature in otherwise healthy eyes as well as a broad spectrum of ocular diseases. The case herein reported Stargardt disease, toxoplasmosis, and high myopia all could potentially contribute to the pathogenesis of these findings. Further studies are needed to define etiologies as well as clinical significance and course of FCEs.
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http://dx.doi.org/10.1177/1120672120932092DOI Listing
June 2020

Telemedicine Follow-Up for Intravitreal Bevacizumab Injection in the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) Cohort.

Clin Ophthalmol 2020 29;14:1161-1163. Epub 2020 Apr 29.

Byers Eye Institute, Horngren Family Vitreoretinal Center, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California.

Telemedicine has emerged as a potential solution to face the disproportion between infants that need to be screened for retinopathy of prematurity (ROP) and the lack of ophthalmologists. We evaluated its utility in the follow-up after off-label intravitreal injection of bevacizumab. None of the treated infants ended up with bad anatomic outcome. Telemedicine is an alternative safe method to monitor patients after treatment.
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http://dx.doi.org/10.2147/OPTH.S250361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200391PMC
April 2020

Retinopathy of prematurity and neurodevelopmental outcomes in premature infants.

Eye (Lond) 2021 Mar 12;35(3):1014-1016. Epub 2020 May 12.

Department of Ophthalmology, Byers Eye Institute, Horngren Family Vitreoretinal Center, Stanford University School of Medicine, Palo Alto, CA, 94303, USA.

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http://dx.doi.org/10.1038/s41433-020-0941-xDOI Listing
March 2021

Von Hippel-Lindau Syndrome Phenotype With Prominent Vitreoretinal Neovascularization Treated With Early PPV: A Case Series and Literature Review.

Ophthalmic Surg Lasers Imaging Retina 2020 02;51(2):109-115

Background And Objective: To describe a case series of three patients in one family with Von Hippel-Lindau (VHL) disease who presented with vitreoretinal neovascularization and resulting tractional retinal detachments (TRDs). This vitreoretinal phenotype of VHL may benefit from early surgical intervention.

Patients And Methods: Descriptive case series of three patients in one family with VHL disease. A review of the literature regarding surgical intervention for VHL was performed.

Results: All three patients developed prominent intravitreal neovascularization with fibrovascular growth within the vitreous secondary to a retinal capillary hemangioma. Two subjects with intravitreal neovascularization were treated with laser and cryotherapy but eventually developed a TRD. The final vision in these two patients was light perception and 20/300. The eye that was preemptively treated with vitrectomy to remove the vitreous sustaining the neovascularization had visual acuity of 20/50 after surgery.

Conclusion: Intravitreal neovascularization with fibrovascular proliferation may be an indication for vitrectomy prior to the development of retinal detachment. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:109-115.].
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http://dx.doi.org/10.3928/23258160-20200129-07DOI Listing
February 2020

Resolution of optic disc pit-associated macular retinoschisis after topical carbonic anhydrase inhibitor treatment: Report of a case.

Eur J Ophthalmol 2020 Feb 4:1120672120904664. Epub 2020 Feb 4.

Byers Eye Institute, Horngren Family Vitreoretinal Center, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Background: Optic disc pits frequently lead to visual deterioration due to macular retinoschisis or serous retinal detachment. Here, we report a case of optic disc pit-associated macular retinoschisis due to intraretinal fluid accumulation that resolved with improvement in visual acuity after treatment with topical dorzolamide.

Case Description: A 56-year-old otherwise healthy female with no ocular history presented with 2 weeks of slowly worsening blurry vision in her right eye. Visual acuity was 20/30 in the right eye. Posterior segment examination revealed posterior vitreous detachment, an optic disc pit at 9 o'clock, macular edema and foveoschisis with fluid extending from the optic nerve, and a normal peripheral retina. Optical coherence tomography imaging of the macula showed central subfield thickness of 526 µm. The patient preferred no surgical intervention, so topical dorzolamide 2% three times daily was initiated. Over the next 2 years, the central subfield thickness steadily declined from 526 to 262 µm, and her vision improved to 20/20 with improvement in the macular retinoschisis.

Conclusion: Our report presents a case of resolution of optic disc pit-associated macular retinoschisis due to intraretinal fluid accumulation with possible role for dorzolamide as a potential treatment option.
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http://dx.doi.org/10.1177/1120672120904664DOI Listing
February 2020

Pentosan Polysulfate Sodium Exposure and Drug-Induced Maculopathy in Commercially Insured Patients in the United States.

Ophthalmology 2020 04 5;127(4):535-543. Epub 2019 Nov 5.

Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California. Electronic address:

Purpose: To determine the association and cumulative dose-response pattern between pentosan polysulfate sodium (PPS) use for interstitial cystitis (IC) and maculopathy.

Design: Large, multicenter, retrospective cohort study of commercially insured patients in the MarketScan database (Truven Health Analytics, San Jose, CA).

Participants: Two hundred twenty-seven thousand three hundred twenty-five patients with IC who were enrolled continuously in the MarketScan database.

Methods: Cox proportional hazards models (controlling for patient gender, age at index diagnosis of IC, and diagnosis with diabetes mellitus) followed up patients from index diagnosis of IC for 5 years, or until patients discontinued insurance coverage, or until patients' first diagnosis with a maculopathy. As a sensitivity analysis, we re-estimate all models after excluding all patients with diabetes. To assess for dose response, we calculated the total days of PPS prescriptions filled and created a categorical variable indicating total exposure.

Main Outcome Measures: The primary outcome measure was association between binary PPS exposure and any maculopathy. Secondary outcome measures included exposure between binary and categorical, time-dependent, exposure to PPS and to drusen, nonexudative age-related macular degeneration (AMD), exudative AMD, hereditary maculopathy, and toxic maculopathy.

Results: The most common diagnoses of maculopathy in patients with IC were exudative AMD (1.5%), drusen (0.8%), nonexudative AMD (0.3%), toxic maculopathy (0.1%), and hereditary dystrophy (0.04%). In unadjusted analyses, the percentage of patients who filled a PPS prescription and were diagnosed later with a maculopathy (2.37%) was very similar to the percentage of patients who did not fill a prescription (2.77%). Survival models using a binary variable indicating PPS exposure showed no significant associations between PPS exposure and diagnosis of drusen, nonexudative AMD, exudative AMD, toxic maculopathy, hereditary dystrophy, or an aggregate variable of any maculopathy. Similarly, there was no dose-dependent relationship between PPS exposure and diagnosis of any maculopathy. These findings remained stable in sensitivity analysis models that excluded patients with diabetes mellitus.

Conclusions: In this large, commercial claims database analysis, no association was found between PPS exposure and subsequent diagnosis of maculopathy.
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http://dx.doi.org/10.1016/j.ophtha.2019.10.036DOI Listing
April 2020

Widefield imaging of retinal and choroidal tumors.

Int J Retina Vitreous 2019 12;5(Suppl 1):49. Epub 2019 Dec 12.

Department of Ophthalmology, Stanford University Byers Eye Institute, 2452 Watson Court MC 5353, Palo Alto, CA 94303 USA.

Background: Wide-field imaging plays an increasingly important role in ocular oncology clinics. The purpose of this review is to describe the commonly used wide-field imaging devices and review conditions seen in ocular oncology clinic that underwent wide-field imaging as part of the multimodal evaluation.

Summary Of Review: Wide-field or wide-angle imaging is defined as greater than 50° field of view. Modern devices can reach far beyond this reporting fields of view up to 267°, when utilizing montage features, with increasingly impressive resolution. Wide-field imaging modalities include fundus photography, fluorescein angiography (FA), fundus autofluorescence (FAF), indocyanine angiography (ICG), spectral domain optical coherence tomography (SD-OCT), and recently wide-field OCT Angiography (OCTA). These imaging modalities are increasingly prevalent in practice. The wide-field systems include laser, optical, and lens based systems that are contact or non-contact lens systems each with its own benefits and drawbacks. The purpose of this review is to discuss commonly used wide-field imaging modalities for retinal and choroidal tumors and demonstrate the use of various widefield imaging modalities in select ocular oncology cases.

Conclusions: Clinical examination remains the gold standard for the evaluation of choroidal and retinal tumors. Wide-field imaging plays an important role in ocular oncology for initial documentation, surgical planning, determining the relationship of the tumor to adjacent ocular structures, following tumor size after treatment, and monitoring for recurrence.
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http://dx.doi.org/10.1186/s40942-019-0196-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907111PMC
December 2019

Colour change in the newborn iris: 2-year follow-up of the Newborn Eye Screening Test study.

Acta Ophthalmol 2020 Jun 6;98(4):e521-e522. Epub 2019 Dec 6.

Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, USA.

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http://dx.doi.org/10.1111/aos.14321DOI Listing
June 2020

Surgical Outcomes Of Rhegmatogenous Retinal Detachment In Young Adults Ages 18-30 Years.

Clin Ophthalmol 2019 31;13:2135-2141. Epub 2019 Oct 31.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

Purpose: The purpose of this study is to investigate associations with and surgical outcomes of rhegmatogenous retinal detachment (RRD) in young adults.

Methods: This is a retrospective consecutive case series of patients aged 18-30 years who underwent surgical repair for RRD between January 1, 2014 and December 1, 2016 at a university referral center.

Results: The current study includes 38 eyes with RRD. Documented high or moderate myopia was present in 28 (74%) eyes. Connective tissue disease was present in 3 (8%) eyes. Median pre-operative visual acuity (VA) was 20/70. Surgery was performed via scleral buckle (SB) alone in 27/38 (71%) and via combined SB and pars plana vitrectomy (SB/PPV) in 11/38 (29%) eyes. Single surgery anatomical success (SSAS) rate was 20/27 (74%) for SB and 7/11 (64%) for SB/PPV. The retina was reattached at last follow-up in 25/27 (93%) for SB and 11/11 (100%) for SB/PPV. The median postoperative VA was 20/40.

Conclusion: In the current study of young adults with RRD, the most common association was high or moderate myopia. Visual and anatomic outcomes at last follow-up were generally favorable.
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http://dx.doi.org/10.2147/OPTH.S213042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827499PMC
October 2019

Retinopathy of Prematurity Reactivated 28 Months after Injection of Ranibizumab.

Ophthalmol Retina 2019 10 9;3(10):913-915. Epub 2019 Jul 9.

Department of Ophthalmology, Catholic University of Sacred Heart, Rome, Italy.

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http://dx.doi.org/10.1016/j.oret.2019.06.017DOI Listing
October 2019

Persistent Plus Disease Subsequent to Panretinal Photocoagulation in an Infant With Retinopathy of Prematurity.

Ophthalmic Surg Lasers Imaging Retina 2019 08;50(8):520-521

Plus disease, or the presence of vascular dilation and tortuosity, is the most reliable predictor of the progression of retinopathy of prematurity (ROP), making resolution of plus disease one of the earliest signs of ROP regression. Patients with certain comorbid conditions such as anemia and cardiovascular disease may have persistent plus-like disease following successful resolution of ROP. The authors present a case of a 24-week premature infant who was treated with panretinal photocoagulation for stage 3, zone II. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:520-521.].
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http://dx.doi.org/10.3928/23258160-20190806-08DOI Listing
August 2019

Birth-related subconjunctival and retinal haemorrhages in the Newborn Eye Screening Test (NEST) Cohort.

Eye (Lond) 2019 11 8;33(11):1819. Epub 2019 Jul 8.

Horngren Family Vitreoretinal Center, Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, 94305, USA.

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http://dx.doi.org/10.1038/s41433-019-0523-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002732PMC
November 2019

Lipid-Lowering Medications Are Associated with Lower Risk of Retinopathy and Ophthalmic Interventions among United States Patients with Diabetes.

Am J Ophthalmol 2019 11 10;207:378-384. Epub 2019 Jun 10.

Department of Ophthalmology, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California, USA. Electronic address:

Purpose: To evaluate the impact of lipid-lowering medications on diabetic retinopathy and diabetic complications requiring intervention in the US population.

Design: Retrospective cohort analysis.

Methods: Administrative insurance claims were drawn from the Truven MarketScan Commercial Claims and Encounters databases. Population consisted of beneficiaries with type 2 diabetes mellitus (T2DM). Main outcome measurements were any signs of diabetic retinopathy, as measured by diagnosis codes for nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), or diabetic macular edema (DME) and procedure codes for retinopathy treatments (anti-VEGF injections, laser therapy, and vitrectomy).

Results: A population of 269,782 patients diagnosed with T2DM between 2008 and 2015 were analyzed. A total of 99,233 patients (37%) were undergoing treatment with lipid-lowering medications. Approximately 6% of patients taking lipid-lowering medications had a diagnosis code for NPDR, PDR, or DME or a procedural code for intravitreal injections, pars plana vitrectomy (PPV) or laser treatment in their record following diagnosis with diabetes compared to 6.5% of patients who did not take lipid-lowering medications (P < 0.01). In adjusted time-to-event analyses, patients who took lipid-lowering medications prior to diagnosis of T2DM were less likely to progress to any retinopathy diagnosis (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.55-0.65) and less likely to receive any treatment for retinopathy (HR, 0.81; 95% CI, 0.78-0.84). These findings were significant at the aggregate level, at the individual level of diagnosis (NPDR HR, 0.63; 95% CI, 0.57-0.69; PDR HR, 0.45; 95% CI, 0.37-0.54; and DME HR, 0.39; 95% CI, 0.33-0.45), and at the level of each treatment category (anti-VEGF injection HR, 0.81; 95% CI, 0.78-0.84; laser HR, 0.62; 95% CI, 0.47-0.81; and vitrectomy HR, 0.71; 95% CI, 0.59-0.85).

Conclusions: This study found consistent evidence that patients taking lipid-lowering medications were less likely to develop NPDR, PDR, or DME and modest evidence that these patients are less likely to receive intravitreal injections of anti-VEGF medication, laser treatments, or vitrectomy. The study validates the findings of studies that have used claims databases in East Asia in relatively homogeneous populations to estimate an association between statin use and retinopathy, replicating them in a US context in a large commercial claims database.
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http://dx.doi.org/10.1016/j.ajo.2019.05.029DOI Listing
November 2019

Bilateral Endophthalmitis after Immediately Sequential Bilateral Cataract Surgery.

Ophthalmol Retina 2019 07 11;3(7):618-619. Epub 2019 Apr 11.

From the Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2019.04.007DOI Listing
July 2019

Optic Nerve Aplasia, Chorioretinal Hypoplasia, and Microcornea After In Utero Infection With Cytomegalovirus.

Ophthalmic Surg Lasers Imaging Retina 2019 05;50(5):e171-e175

Optic nerve aplasia (ONA) is a rare phenomenon characterized by absence of the optic nerve, retinal blood vessels, and retinal ganglion cells. The authors report a case of optic nerve aplasia in association with congenital cytomegalovirus (CMV) infection, conveyed through multimodal imaging including color fundus photography, fluorescein angiography, and B-scan ultrasonography. Furthermore, the authors review the common ocular findings and previously reported cases of ONA in congenital CMV infection. Screening and counseling can be performed to advise parents about the potential risks and severity of this rare clinical manifestation. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e171-e175.].
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http://dx.doi.org/10.3928/23258160-20190503-18DOI Listing
May 2019

MUST Beg to Differ.

Ophthalmic Surg Lasers Imaging Retina 2019 05;50(5):266-268

The authors provide a significant interpretation of the National Eye Institute-sponsored Multicenter Uveitis Steroid Treatment study, in which patients with severe, non-infectious intermediate, posterior, or panuveitis were randomly assigned to receive local treatment using the sutured intravitreal fluocinolone acetonide implant or systemic treatment consisting of oral steroids and conventional steroid-sparing immunosuppression, with a primary outcome of visual acuity at 2 years of follow-up. The authors also present evidence-based guidance for the treatment of noninfectious posterior segment involving uveitis. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:266-268.].
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http://dx.doi.org/10.3928/23258160-20190503-01DOI Listing
May 2019

Inflammatory myofibroblastic tumour presenting as a medial eyelid mass in a child.

Can J Ophthalmol 2018 12 17;53(6):e241-e244. Epub 2018 Feb 17.

University of Miami Miller School of Medicine, Miami, Fla. Electronic address:

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http://dx.doi.org/10.1016/j.jcjo.2018.01.018DOI Listing
December 2018

A Spectrum of Regression Following Intravitreal Bevacizumab in Retinopathy of Prematurity.

Am J Ophthalmol 2019 02 9;198:63-69. Epub 2018 Oct 9.

Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA. Electronic address:

Purpose: To describe an improved understanding of the regression patterns following off-label intravitreal bevacizumab (IVB) treatment for retinopathy of prematurity (ROP).

Design: Retrospective cohort study.

Methods: All infants treated with IVB for type 1 ROP at a single institution from June 2013 to March 2018 were retrospectively reviewed and the amount of retinal nonperfusion on fluorescein angiogram was calculated.

Results: In the 92 eyes of 46 patients analyzed, only 3 eyes (3.3%) reached full vascular maturity. Of the 89 eyes not reaching maturity, 39 eyes (43.8%) had vascular arrest alone (VAA), 34 eyes (38.2%) had vascular arrest with persistent tortuosity (VAT), and 16 eyes (18.0%) had ROP reactivation. Those eyes that reactivated were more likely to be initially classified as having aggressive posterior ROP (P = .004) and of Asian ethnicity (P = .008). There were greater areas of ischemia in eyes with reactivation as compared to VAT and VAA (112.1 mm vs 72.5 mm vs 56.6 mm, respectively, P = .007). Younger gestational age at birth was found to be an independent predictor of persistent tortuosity (VAT vs VAA) in a logistic regression model.

Conclusions: Incomplete vascularization following IVB is very common and is associated with a younger gestational age at birth, Asian ethnicity, and aggressive posterior ROP. The presence of tortuosity following IVB may be indicative of persistently elevated vascular endothelial growth factor levels and an early indicator of potential reactivation.
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http://dx.doi.org/10.1016/j.ajo.2018.09.039DOI Listing
February 2019

INTERNAL LIMITING MEMBRANE PEELING DURING PARS PLANA VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT: Cost Analysis, Review of the Literature, and Meta-analysis.

Retina 2018 Oct;38(10):2081-2087

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.

Purpose: To evaluate the visual and potential economic impact of primary internal limiting membrane (ILM) peeling in primary treatment of rhegmatogenous retinal detachment.

Methods: A PubMed search was performed to extract data regarding the rate of epiretinal membrane formation and the rate of secondary pars plana vitrectomy with membrane peel after repair of rhegmatogenous retinal detachment with or without ILM peeling. Data were aggregated and analyzed in a meta-analysis. This information was used to perform a cost analysis to determine the economic ramifications of primary ILM peeling.

Results: Six included studies compared the outcomes of eyes receiving pars plana vitrectomy for rhegmatogenous retinal detachment repair with and without primary ILM peel. The cumulative rate of epiretinal membrane formation was 29% (86/295) in the eyes without ILM peel and 3% (8/289) in the eyes with ILM peel. The cumulative rate of secondary pars plana vitrectomy/membrane peel was 16% (22/141) in the eyes without ILM peel and 0% (0/158) in the eyes with ILM peel. The weighted summary point estimate odds ratio was 0.083 (95% confidence interval 0.042-0.164), indicating a statistically significant protective effect across the 6 studies of ILM peeling and the development of epiretinal membrane. Based on published data, the average dollars saved by conducting a primary ILM peel was $615 in a facility setting and $364 in an ambulatory surgical center.

Conclusion: Published, mainly retrospective, data suggest that primary ILM peel in rhegmatogenous retinal detachment repair may have a significant reduction in the rate of postoperative epiretinal membrane and may lessen the need for secondary pars plana vitrectomy/membrane peel. Furthermore, from an economic perspective, the reduction in the need for secondary surgery may justify the higher cost with primary ILM peel.
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http://dx.doi.org/10.1097/IAE.0000000000002248DOI Listing
October 2018