Publications by authors named "Kimberly A Drenser"

84 Publications

Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes.

Sci Rep 2021 Mar 2;11(1):4966. Epub 2021 Mar 2.

Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, 3375 SW Terwilliger Boulevard, Portland, OR, 97239, USA.

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease affecting premature infants. In addition to prematurity itself and oxygen treatment, genetic factors have been suggested to predispose to ROP. We aimed to identify potentially pathogenic genes and biological pathways associated with ROP by analyzing variants from whole exome sequencing (WES) data of premature infants. As part of a multicenter ROP cohort study, 100 non-Hispanic Caucasian preterm infants enriched in phenotypic extremes were subjected to WES. Gene-based testing was done on coding nonsynonymous variants. Genes showing enrichment of qualifying variants in severe ROP compared to mild or no ROP from gene-based tests with adjustment for gestational age and birth weight were selected for gene set enrichment analysis (GSEA). Mean BW of included infants with pre-plus, type-1 or type 2 ROP including aggressive posterior ROP (n = 58) and mild or no ROP (n = 42) were 744 g and 995 g, respectively. No single genes reached genome-wide significance that could account for a severe phenotype. GSEA identified two significantly associated pathways (smooth endoplasmic reticulum and vitamin C metabolism) after correction for multiple tests. WES of premature infants revealed potential pathways that may be important in the pathogenesis of ROP and in further genetic studies.
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http://dx.doi.org/10.1038/s41598-021-83552-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925531PMC
March 2021

CLINICAL OUTCOMES AND TREATMENT COURSE OF EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FOLLOWING THE DEVELOPMENT OF ENDOPHTHALMITIS.

Retina 2021 Jun;41(6):1242-1250

Associated Retinal Consultants, PC., Department of Ophthalmology, Oakland University William Beaumont School of Medicine, Royal Oak, MI.

Purpose: To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections.

Methods: Multicenter, retrospective series.

Results: From April 2013 to October 2018, 196,598 intravitreal anti-vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P < 0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P < 0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P < 0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumab > bevacizumab; P < 0.001).

Conclusion: Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.
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http://dx.doi.org/10.1097/IAE.0000000000002998DOI Listing
June 2021

PERIPHERAL RETINAL ANGIOGRAPHIC FINDINGS IN MACULAR TELANGIECTASIS TYPE 2.

Retina 2021 Mar;41(3):480-486

Associated Retinal Consultants, PC, Department of Ophthalmology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan.

Purpose: To evaluate the retinal periphery in patients with idiopathic juxtafoveal telangiectasis or macular telangiectasis Type 2 (MacTel2), using widefield fluorescein angiography.

Methods: Single-center, retrospective, observational case series of 50 eyes of 50 patients with MacTel2 and 50 eyes of 50 age-matched controls.

Results: Thirty-seven eyes in the MacTel2 group (74%) showed peripheral capillary nonperfusion or dropout, compared with 37 eyes in the control group (74%, P = 1.0). Morphologically, the MacTel2 group trended toward having a higher proportion of pruning-type capillary dropout (44%) compared with controls (28%), but this was not statistically significant (P = 0.12). Patients with MacTel2 had a higher incidence of microaneurysms compared with controls (MacTel2 56%; controls 42%; P = 0.048), independent of age or systemic risk factors. There was no difference in the incidence of venous-venous shunts (MacTel2 10%; controls 10%; P = 1.0), arteriovenous shunts (MacTel2 14%; controls 18%; P = 0.60), venous tortuosity (MacTel2 60%; controls 66%; P = 0.58), or arterial tortuosity (MacTel2 54%; controls 68%; P = 0.20), which was mild in most cases.

Conclusion: We note a high incidence of peripheral vascular and retinal findings in both patients with MacTel2 and age-matched controls, using widefield fluorescein angiography. Patients with MacTel2 had significantly more microaneurysms, independent of age or other systemic risk factors.
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http://dx.doi.org/10.1097/IAE.0000000000002981DOI Listing
March 2021

The retina revolution: signaling pathway therapies, genetic therapies, mitochondrial therapies, artificial intelligence.

Curr Opin Ophthalmol 2020 May;31(3):207-214

William Beaumont Hospital, Royal Oak.

Purpose Of Review: The aim of this article is to review and discuss the history, current state, and future implications of promising biomedical offerings in the field of retina.

Recent Findings: The technologies discussed are some of the more recent promising biomedical developments within the field of retina. There is a US Food and Drug Administration-approved gene therapy product and artificial intelligence device for retina, with many other offerings in the pipeline.

Summary: Signaling pathway therapies, genetic therapies, mitochondrial therapies, and artificial intelligence have shaped retina care as we know it and are poised to further impact the future of retina care. Retina specialists have the privilege and responsibility of shaping this future for the visual health of current and future generations.
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http://dx.doi.org/10.1097/ICU.0000000000000656DOI Listing
May 2020

ETIOLOGY AND CLINICAL CHARACTERISTICS OF MACULAR EDEMA IN PATIENTS WITH FAMILIAL EXUDATIVE VITREORETINOPATHY.

Retina 2020 Jul;40(7):1367-1373

Department of Ophthalmology, William Beaumont School of Medicine, Associated Retinal Consultants, Royal Oak, Michigan.

Purpose: To describe the etiology and clinical characteristics of macular edema (ME) in patients with familial exudative vitreoretinopathy.

Methods: Observational, retrospective case series of 30 patients (34 eyes) with ME and familial exudative vitreoretinopathy who underwent spectral-domain optical coherence tomography imaging between 2009 and 2016. Baseline and follow-up optical coherence tomographies were correlated with color fundus photography and fluorescein angiography.

Results: The average age was 20.6 years (6.6-68.7). Eighteen eyes exhibited cystoid ME (52.9%), 14 noncystoid ME (41.2%), and 2 eyes (5.9%) with both. Macular edema was foveal in 52.9% (n = 18). Eighteen of 24 eyes (64.3%) with an available fluorescein angiography showed leakage from ME. The most common structural feature was posterior hyaloidal organization/contraction (n = 15). Sixteen eyes were treated with topical or intravitreal steroids (n = 6), intravitreal anti-vascular endothelial growth factor (n = 3), or pars plana vitrectomy with membrane stripping (n = 7). There was no difference between mean preoperative and postoperative LogMAR visual acuity (0.63 [20/85] vs. 0.87 [20/148], P = 0.35) after vitrectomy despite a statistical improvement in the mean central foveal thickness (596 mm vs. 303 mm, P = 0.04).

Conclusion: Macular edema in familial exudative vitreoretinopathy occurs most commonly because of traction. Vitrectomy is effective for relieving tractional forces with anatomical improvement.
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http://dx.doi.org/10.1097/IAE.0000000000002623DOI Listing
July 2020

Surgical Management of Suprachoroidal Hemorrhage in Younger Patients.

Ophthalmic Surg Lasers Imaging Retina 2019 07;50(7):454-458

Suprachoroidal hemorrhage (SCH) is a rare but serious complication that may accompany nearly any ocular surgery. In contrast to SCH in adults, the incidence and management of SCH in the pediatric population is poorly defined. Herein, the authors describe their experience managing SCH in patients of a younger age group, characterize this rare complication using multimodal imaging, and review the current literature on the subject. In this retrospective case series, two patients developed intraoperative SCH during cataract extraction once rendered aphakic. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:454-458.].
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http://dx.doi.org/10.3928/23258160-20190703-08DOI Listing
July 2019

Correlating Changes in the Macular Microvasculature and Capillary Network to Peripheral Vascular Pathologic Features in Familial Exudative Vitreoretinopathy.

Ophthalmol Retina 2019 07 4;3(7):597-606. Epub 2019 Mar 4.

Department of Ophthalmology, Shiley Eye Institute and Jacobs Retina Center, University of California, San Diego, La Jolla, California. Electronic address:

Purpose: To evaluate the macular microvasculature in patients with familial exudative vitreoretinopathy (FEVR) using OCT angiography (OCTA) and to assess for peripheral vascular changes using widefield fluorescein angiography (WFA).

Design: Multicenter, retrospective, comparative, observational case series.

Participants: We identified 411 patients with FEVR, examined between September 2014 and June 2018. Fifty-seven patients with FEVR and 60 healthy controls had OCTA images of sufficient quality for analysis.

Methods: Custom software was used to assess for layer-specific, quantitative changes in vascular density and morphologic features on OCTA by way of vessel density (VD), skeletal density (SD), fractal dimension (FD), vessel diameter index (VDI), and foveal avascular zone (FAZ). Widefield fluorescein angiography images were reviewed for peripheral vascular changes including capillary dropout, late-phase angiographic posterior and peripheral vascular leakage (LAPPEL), vascular dragging, venous-venous shunts, and arteriovenous shunts.

Main Outcome Measures: Macular microvascular parameters on OCTA and peripheral angiographic findings on WFA.

Results: OCT angiography analysis of 117 patients (187 eyes; 92 FEVR patients and 95 control participants) demonstrated significantly reduced VD, SD, and FD and greater VDI in patients with FEVR compared with controls in the nonsegmented retina, superficial retinal layer (SRL), and deep retinal layer (DRL). The FAZ was larger compared with that in control eyes in the DRL (P < 0.0001), but not the SRL (P = 0.52). Subanalysis by FEVR stage showed the same microvascular changes compared with controls for all parameters. Widefield fluorescein angiography analysis of 95 eyes (53 patients) with FEVR demonstrated capillary nonperfusion in all eyes: 47 eyes (49.5%) showed LAPPEL, 32 eyes (33.7%) showed vascular dragging, 30 eyes (31.6%) had venous-venous shunts, and 33 eyes (34.7%) had arteriovenous shunts. Decreasing macular VD on OCTA correlated with increasing peripheral capillary nonperfusion on WFA. Decreasing fractal dimension on OCTA correlated with increasing LAPPEL severity on WFA.

Conclusions: Patients with FEVR demonstrated abnormalities in the macular microvasculature and capillary network, in addition to the peripheral retina. The macular microvascular parameters on OCTA may serve as biomarkers of changes in the retinal periphery on WFA.
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http://dx.doi.org/10.1016/j.oret.2019.02.013DOI Listing
July 2019

Late re-activation of Coats disease.

Am J Ophthalmol Case Rep 2019 Sep 25;15:100458. Epub 2019 Apr 25.

Associated Retinal Consultants, William Beaumont Hospital, Royal Oak, MI, USA.

Purpose: To report case of Coats disease with the longest known interval of disease quiescence prior to first reactivation (17 years).

Observation: A 25-year-old male was regularly followed for Coats disease since age 4. After initial treatment with cryoablation, disease quiescence was achieved at age 8. The disease activity was well controlled for 17 years after which he developed decreased vision in the right eye at age 25. Late reactivation of Coats disease was diagnosed and multiple treatments ensued. Despite aggressive therapy, the patient experienced progressive exudation warranting surgical management and eventually developed neovascular glaucoma.

Conclusion: Once diagnosed with Coats disease, lifelong monitoring is essential to early detection and treatment of potential disease reactivation. The interval between disease quiescence and reactivation is variable, with this case representing the longest known interval of disease quiescence prior to first reactivation (17 years).
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http://dx.doi.org/10.1016/j.ajoc.2019.100458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518316PMC
September 2019

Diagnosis and Management of Familial Exudative Vitreoretinopathy: A Lifelong, Progressive, and Often Asymmetric Disease.

JAMA Ophthalmol 2019 Sep;137(9):1059-1060

Associated Retinal Consultants PC, Royal Oak, Michigan.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.1484DOI Listing
September 2019

Characterization of Epiretinal Proliferation in Full-Thickness Macular Holes and Effects on Surgical Outcomes.

Ophthalmol Retina 2019 08 1;3(8):694-702. Epub 2019 Apr 1.

Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts; Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that classically is associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterized macular hole-associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes.

Design: Multicenter, interventional, retrospective case-control study.

Participants: Consecutive eyes that underwent surgery for FTMH with a minimum of 12 months follow-up.

Methods: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane (ILM) peeling. Spectral-domain OCT imaging was obtained before and after surgery.

Main Outcome Measures: Improvement in visual acuity and single-surgery hole closure rates in eyes with, versus without, MHEP at 12 months.

Results: Seven hundred twenty-five charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) showed MHEP. Patients with FTMH and MHEP were older (P < 0.002) and more often men (P = 0.001), and showed more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). Twelve months after surgery, FTMH with MHEP patients showed significantly less improvement in visual acuity (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with 1 surgery compared to FTMH without MHEP (26.7% vs. 4.8%; P = 0.002]). Peeling the ILM was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariate testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031) and for single-surgery nonclosure (P = 0.009) and that ILM peeling improved single-surgery closure rates (P = 0.026).

Conclusions: We found that FTMH with MHEP showed poorer anatomic and visual outcomes after vitrectomy compared with FTMH without MHEP. Internal limiting membrane peeling was associated with improved closure rates and should be considered when MHEP is detected before surgery.
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http://dx.doi.org/10.1016/j.oret.2019.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684822PMC
August 2019

Adult Coats' Disease, Dubin-Johnson Syndrome, and the Search for Targeted Therapies.

Ophthalmic Surg Lasers Imaging Retina 2019 05;50(5):318-321

Coats' disease is nonhereditary retinal vascular disorder characterized by telangiectatic retinal vessels with prominent aneurysmal changes and exudation. A conclusive etiology has not yet been determined. In this retrospective case report and literature review, a 64-year-old male with Dubin-Johnson syndrome presented with unilateral retinal vascular changes and exudation consistent with a diagnosis of adult Coats' disease. The authors conclude that patients with Dubin-Johnson syndrome carry mutations in a multidrug resistance associated protein (MRP). MRPs are also expressed in the retina, retinal pigment epithelium, and vascular endothelium, where they export toxins and metabolites, and may serve as a therapeutic target. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:318-321.].
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http://dx.doi.org/10.3928/23258160-20190503-10DOI Listing
May 2019

Ocular Hypertension in Adults with a History of Prematurity.

Ophthalmol Retina 2018 06 1;2(6):629-635. Epub 2017 Dec 1.

Associated Retinal Consultants P.C., Royal Oak, Michigan; Oakland University William Beaumont School of Medicine, Department of Ophthalmology, Royal Oak, Michigan. Electronic address:

Purpose: To determine the ocular hypertension (OHT) incidence in patients with a history of prematurity and the effect of intervention for acute retinopathy of prematurity (ROP) in infancy on OHT incidence.

Design: Retrospective case series at a single tertiary referral vitreoretinal practice.

Participants: A total of 407 eyes of 213 patients were included, with ROP stage 0 to 5.

Methods: A retrospective chart review was conducted of patients aged ≥15 years, seen from 1973 to 2013, with a history of premature birth (gestational age <32 weeks). Data were collected from patient charts, including gender, date of birth, gestational age at birth, birth weight, stage of ROP at presentation, management (including laser, cryotherapy, lens-sparing vitrectomy [LSV], or lensectomy-vitrectomy). Ocular hypertension (if present) data included age of onset, timing of glaucoma surgery (if performed), lens status, and last follow-up examination.

Main Outcome Measures: Development of OHT, defined as eyes requiring a glaucoma medication for more than 6 consecutive months or surgical intervention for elevated intraocular pressure.

Results: Of included eyes, 155 (38.1%) developed OHT within 69 years of follow-up. Subgroup analyses revealed an OHT incidence of 23.2% (36/155 eyes) in eyes without a history of any treatment for acute ROP (spontaneously regressed), 23.3% (10/43 eyes) in eyes that underwent ablative therapy alone, and 58.5% (76/130 eyes) in eyes requiring acute incisional retinal surgery (P < 0.01). Stage 4 eyes had a lower OHT incidence compared with stage 5 eyes (40.5% [17/42] vs. 66.7% [54/81], P < 0.01); however, among stage 4 and stage 5 eyes, phakic eyes at last follow-up had a decreased OHT incidence compared with aphakic eyes (27.8% [5/18] vs. 69.8% [60/86], P < 0.01).

Conclusions: Patients with a history of extreme prematurity are at an increased risk of OHT and glaucoma, even if they did not receive acute ROP treatment. More severe acute ROP is associated with higher incidence of OHT, and this is associated with an increased incidence of incisional surgical intervention. Awareness of the increased lifelong risk of adverse ocular sequelae in patients with a history of prematurity will help guide appropriate monitoring.
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http://dx.doi.org/10.1016/j.oret.2017.10.005DOI Listing
June 2018

Longitudinal Examination of Fellow-Eye Vascular Anomalies in Coats' Disease With Widefield Fluorescein Angiography: A Multicenter Study.

Ophthalmic Surg Lasers Imaging Retina 2019 04;50(4):221-227

Background And Objective: Retinovascular anomalies in the fellow eyes of patients with Coats' disease have been described, but the clinical significance is unknown, as well as whether these lesions progress over time.

Patients And Methods: This is an international, multicenter, retrospective, observational cohort study of fellow-eye abnormalities on widefield fluorescein angiography in patients with Coats' disease.

Results: Three hundred fifty eyes of 175 patients with Coats' disease were analyzed. A total of 33 patients (18.8%) demonstrated abnormal fellow-eye findings: 14 (42.4%) telangiectasias, 18 (54.5%) aneurysms, six (18.2%) segmental non-perfusion, six (18.2%) leakage, and two (6.0%) vascular tortuosity. All eyes were asymptomatic, and none of the lesions progressed over time. There was no association between fellow-eye findings with severity of Coats' disease (P = .16), patient age (P = .16), or presence of systemic vascular disease (P = .16).

Conclusions: The vascular abnormalities in fellow eyes of patients with Coats' disease did not progress over time. Observation is a reasonable initial management strategy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:221-227.].
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http://dx.doi.org/10.3928/23258160-20190401-04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615457PMC
April 2019

Vessel Tortuosity Cutoff Values Using the Modified ROPtool May Predict Need for Treatment in Retinopathy of Prematurity.

Ophthalmic Surg Lasers Imaging Retina 2019 04;50(4):215-220

Background And Objective: To quantify vessel tortuosity among infants with retinopathy of prematurity (ROP).

Patients And Methods: This was a retrospective study including 61 RetCam images from 33 infants. The laser treatment (LT) group included 17 infants who underwent laser for ROP. The no-treatment (NT) group included 16 infants. The modified ROPtool was used to calculate mean vessel tortuosity (MVT) and highest vessel tortuosity (HVT) for the participants and for the standard plus disease photograph from the Early Treatment for Retinopathy of Prematurity (ETROP) study.

Results: The median MVT was 1.226 versus 1.056 for the LT and NT groups, respectively (P < .001). The median HVT was 1.346 versus 1.088 (P < .001). An MVT of 1.124 was 96.7% sensitive and 100% specific for identifying infants with treatment-requiring ROP. Both MVT and HVT cutoff values correctly captured plus disease in the standard ETROP trial photograph.

Conclusion: The modified ROPtool can be used to identify infants who have treatment-requiring ROP with a high level of sensitivity and specificity. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:215-220.].
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http://dx.doi.org/10.3928/23258160-20190401-03DOI Listing
April 2019

The Natural History of Congenital X-Linked Retinoschisis and Conversion between Phenotypes over Time.

Ophthalmol Retina 2019 01 24;3(1):77-82. Epub 2018 Aug 24.

Associated Retinal Consultants, William Beaumont Hospital, Royal Oak, Michigan; William Beaumont School of Medicine, Oakland University, Rochester, Michigan. Electronic address:

Purpose: To evaluate the natural history of congenital X-linked retinoschisis (CXLRS) and to assess disease stability or progression over time.

Design: Retrospective case series at a single-center, tertiary care, pediatric retina practice.

Participants: One hundred two eyes of 51 patients with CXLRS.

Methods: The clinical examinations, fundus photographs, and OCT images of all patients with CXLRS were assessed. Eyes that initially demonstrated combined retinoschisis-retinal detachments and those with large, centrally overhanging schisis cavities were excluded from the analysis (n = 49) because they underwent surgery, which precluded observation of the natural disease course.

Main Outcome Measures: Stability or conversion of CXLRS phenotype over time.

Results: Fifty-three eyes met inclusion criteria for observation of natural disease history over time. At the time of diagnosis, 7.5% of eyes showed type 1 disease (n = 4), 17% showed type 2 disease (n = 9), 66% showed type 3 disease (n = 35), and 9.5% showed type 4 disease (n = 5). Mean length of follow-up was 7.4 years. A total of 7.5% of eyes demonstrated a combined retinoschisis-retinal detachment requiring surgery (n = 4), whereas 1.8% demonstrated a large, centrally overhanging schisis cavity requiring surgery (n = 1). Overall, 83% of eyes (n = 44) remained the same type without conversion or development of a complication requiring surgery. The remaining 17% of eyes (n = 9) experienced some type of change from their baseline diagnosis, with 7.5% (n = 4) converting between phenotypes and 9.5% (n = 5) demonstrating a complication requiring surgery; 3.75% of eyes (n = 2) converted from type 2 to 3 and 7.5% of eyes (n = 4) converted from type 3 to a combined retinoschisis-retinal detachment with mean time to conversion of 4.07 years.

Conclusions: This longitudinal study conveyed the natural history of CXLRS. Congenital X-linked retinoschisis displayed long-term stability in 83% of eyes with conversion or progression of the disease to a more severe phenotype in the remaining cases. Type 3 CXLRS was a risk factor for the development of a combined retinoschisis-retinal detachment and may benefit from closer follow-up.
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http://dx.doi.org/10.1016/j.oret.2018.08.006DOI Listing
January 2019

Predictors of Endophthalmitis after Intravitreal Injection: A Multivariable Analysis Based on Injection Protocol and Povidone Iodine Strength.

Ophthalmol Retina 2019 01 25;3(1):3-7. Epub 2018 Sep 25.

Associated Retinal Consultants, PC, William Beaumont Hospital, Royal Oak, Michigan; William Beaumont School of Medicine, Oakland University, Rochester, Michigan. Electronic address:

Purpose: To determine the incidence of endophthalmitis after anti-vascular endothelial growth factor (VEGF) therapy at our institution and to identify potential risk factors for endophthalmitis occurring after injection.

Design: Retrospective, single-center cohort study.

Participants: All patients who received an intravitreal injection of an anti-VEGF medication between January 1, 2014, and March 31, 2017.

Methods: Current Procedural Terminology and International Classification of Diseases billing codes were used to identify instances of anti-VEGF administration and cases of endophthalmitis. Medical records and injection technique were reviewed carefully in each case. Multivariable logistic regression analysis was performed in a stepwise fashion to determine independent predictors of endophthalmitis based on injection protocol.

Main Outcome Measures: Incidence of endophthalmitis after injection and odds of endophthalmitis by injection technique with 95% confidence intervals (CIs).

Results: A total of 154 198 anti-VEGF injections were performed during the period of interest, resulting in 58 cases of endophthalmitis (0.038% [1:2659]). After adjustment for confounders, both 2% lidocaine jelly (odds ratio [OR], 11.28; 95% CI, 3.39-37.46; P < 0.001) and 0.5% Tetravisc (Ocusoft, Richmond, TX; OR, 3.95; 95% CI, 1.15-13.50; P = 0.03) use were independent risk factors for endophthalmitis after injection. Lid speculum use, povidone iodine strength (5% vs. 10%), injection location (superior or inferior), conjunctival displacement, use of provider gloves, use of a strict no-talking policy, use of subconjunctival lidocaine, and topical antibiotic use were not statistically significant predictors of endophthalmitis after injection. There was no difference in endophthalmitis rate among the anti-VEGF agents (bevacizumab, ranibizumab 0.3 mg, ranibizumab 0.5 mg, and aflibercept).

Conclusions: The incidence of endophthalmitis after anti-VEGF injections is low. Use of lidocaine jelly or Tetravisc may increase the risk of endophthalmitis after injection.
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http://dx.doi.org/10.1016/j.oret.2018.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597000PMC
January 2019

Fellow Eye Anti-VEGF 'Crunch' Effect in Retinopathy of Prematurity.

Ophthalmic Surg Lasers Imaging Retina 2018 09;49(9):e102-e104

Background And Objective: Anti-vascular endothelial growth factor (VEGF) therapy is increasing in popularity for treatment of retinopathy of prematurity (ROP). Despite many technical benefits, issues remain prompting further investigation.

Patients And Methods: Retrospective case report and literature review.

Results: A 42-week-old postmenstrual age female with gestational age of 28 weeks and birth weight of 990 g presented with prominent progression of peripapillary purely tractional atypical stage 4A ROP in both eyes following intravitreal bevacizumab therapy in the right eye only.

Conclusion: The authors present the first reported case, to their knowledge, of a "crunch" phenomenon tractional retinal detachment from fellow eye administration of bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e102-e104.].
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http://dx.doi.org/10.3928/23258160-20180907-16DOI Listing
September 2018

Considerations for ophthalmic applications of optogenetics.

Acta Ophthalmol 2018 Dec 31;96(8):e1037. Epub 2018 May 31.

Associated Retinal Consultants, William Beaumont Hospital, Royal Oak, Michigan, USA.

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http://dx.doi.org/10.1111/aos.13779DOI Listing
December 2018

Genetic Testing for Retina Specialists.

Ophthalmic Surg Lasers Imaging Retina 2018 05;49(5):292-295

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http://dx.doi.org/10.3928/23258160-20180501-01DOI Listing
May 2018

Congenital X-Linked Retinoschisis: An Updated Clinical Review.

Asia Pac J Ophthalmol (Phila) 2018 May-Jun;7(3):169-175. Epub 2018 Apr 9.

Associated Retinal Consultants, Royal Oak, Michigan.

We present an updated clinical review of the pathophysiology, progression, and current treatments in pediatric patients with congenital X-linked retinoschisis (CXLRS). CXLRS is an X-linked inherited retinal degeneration characterized by splitting of the superficial layers of the retina. Most recent classification divides CXLRS into 4 distinct clinical phenotypes: type 1, foveal; type 2, foveolamellar; type 3, complex; and type 4, foveoperipheral. The majority of retinoschisis cavities remain stable throughout life and may spontaneously collapse. However, a select number of patients progress to macula-involving peripheral retinoschisis, rhegmatogenous, and combined tractional-rhegmatogenous detachments that require further intervention. Although several advances have been made over the past several decades, medical therapy remains limited to case series‒based carbonic anhydrase therapy and prophylactic laser retinopexy. Recent advances in genetic-based clinical trials with the retinoschisis gene are promising. Vitreoretinal surgical approaches remain complex, case-based, and require careful planning depending on the configuration and location of the retinoschisis cavity.
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http://dx.doi.org/10.22608/APO.201803DOI Listing
June 2018

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING OF THE MACULA AND VITREOMACULAR INTERFACE IN PERSISTENT FETAL VASCULATURE SYNDROME WITH POSTERIOR INVOLVEMENT.

Retina 2019 Mar;39(3):581-586

Associated Retinal Consultants, William Beaumont Hospital, Royal Oak, Michigan.

Purpose: To describe the microstructural features of the macula and vitreomacular interface in persistent fetal vasculature syndrome (PFVS) with posterior involvement managed with early vitrectomy or with observation, with functional correlation.

Methods: We retrospectively identified 45 consecutive pediatric patients with PFVS with posterior involvement treated from 2005 to 2016. The eyes that could be imaged with spectral domain optical coherence tomography were included, and images were correlated with best-corrected visual acuity.

Results: Thirty-eight imaging sessions were performed on 10 eyes from 9 patients, including 7 that had been managed with vitrectomy for PFVS-related tractional retinal detachment, and 3 that had been observed. Mean age of the patients who were imaged was 9.1 years and their average length of follow-up was 5.9 years. Best-corrected visual acuities of the eyes imaged ranged from 20/30 to count fingers, with mean best-corrected visual acuity 20/163. All eyes imaged had microstructural anomalies identified. The main anomalous features included posterior hyaloidal organization, vitreoretinal traction, vitreopapillary traction, diminished foveal contour, foveal displacement, and disruption of the ellipsoid zone. Posterior hyaloidal organization (P = 0.043), diminished foveal contour (P = 0.019), and disruption of the ellipsoid zone (P = 0.014) were associated with worse best-corrected visual acuity.

Conclusion: Macular and vitreomacular interface anomalies were identified in all pediatric patients with posterior PFVS imaged with spectral domain optical coherence tomography. These microstructural findings, together with functional measures, may inform the diagnosis and management of PFVS with posterior involvement.
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http://dx.doi.org/10.1097/IAE.0000000000001993DOI Listing
March 2019

Choroidal neovascular membrane in paediatric patients: clinical characteristics and outcomes.

Br J Ophthalmol 2018 09 7;102(9):1232-1237. Epub 2017 Dec 7.

Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.

Purpose: To analyse the clinical characteristics and treatment outcomes of choroidal neovascular membranes (CNVM) in paediatric subjects at three paediatric retina referral centres.

Methods: Medical charts of patients aged 18 years or less with a diagnosis of CNVM were retrospectively reviewed. The demographic profile, laterality, presenting complaint, corrected vision, underlying pathology, fundus, fundus fluorescein angiogram and optical coherence tomogram (OCT) were analysed. CNVM type, frequency, treatment indications, recurrences and final visual acuity were noted.

Results: There were a total of 35 subjects (43 eyes) with a mean age of 11.2 years. The CNVMs were mostly type 2 (90.0%), classic (90.9%), subfoveal (59.09%) and active (84.1%). Best vitelliform macular dystrophy was found to be the most common association (32.5%). Intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent was the initial therapy of choice in all. Eyes with CNVMs responsive to anti-VEGF alone required a mean of 2.11 injections. Patients with recurrent disease (21.21%) had an average of 1.14 episodes per eye. While 50% of recurrent CNVMs stabilised with repeat anti-VEGF treatment, the remaining patients required photodynamic therapy, laser or surgery.

Conclusion: Paediatric CNVMs in this series differed from those in the adult population with regard to aetiology, OCT and angiographic characteristics, treatment response and rate of recurrence.
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http://dx.doi.org/10.1136/bjophthalmol-2017-310497DOI Listing
September 2018

Ocular coherence tomography image data of the retinal laminar structure in a mouse model of oxygen-induced retinopathy.

Data Brief 2017 Dec 6;15:491-495. Epub 2017 Oct 6.

Pediatric Retinal Research Laboratory, Eye Research Institute, Oakland University, Rochester, MI 48309, United States.

The data presented in this article are related to the research paper entitled "Norrin treatment improves ganglion cell survival in an oxygen-induced model of retinal ischemia" (Dailey et al., 2017) [1] This article describes treatment with the human Norrin protein, an atypical Wnt-protein, to improve the survival of retinal ganglion cells in a murine model of Oxygen-Induced Retinopathy (OIR). That study utilized Optical coherence tomography (OCT) to visualize retinal layers at high resolution , and to quantify changes to nerve fiber layer thickness. Organization of the laminar structure of other retinal layers in this model , were not known because of uncertainties regarding potential artifacts during the processing of tissue for traditional histology. The OCT image data provided here shows researchers the retinal laminar structural features that exist in this popular mouse OIR model. Traditional H&E stained retinal tissue sections are also provided here for comparison.
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http://dx.doi.org/10.1016/j.dib.2017.09.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647464PMC
December 2017

Norrin treatment improves ganglion cell survival in an oxygen-induced retinopathy model of retinal ischemia.

Exp Eye Res 2017 11 18;164:129-138. Epub 2017 Aug 18.

Pediatric Retinal Research Laboratory, Eye Research Institute, Oakland University, Rochester Hills, MI 48309, United States; Control of Gene Expression Laboratory, Eye Research Institute, Oakland University, United States. Electronic address:

Treatment of a mouse model of oxygen-induced retinopathy (OIR) with recombinant human Norrin (Norrie Disease Protein, gene: NDP) accelerates regrowth of the microvasculature into central ischemic regions of the neural retina, which are generated after treatment with 75% oxygen. While this reduces the average duration and severity of ischemia overall, we do not know if this accelerated recovery of the microvasculature results in any significant survival of retinal ganglion cells (RGCs). The purpose of this study was to investigate ganglion cell survival with and without the intravitreal injection of Norrin in the murine model of oxygen induced retinopathy (OIR), using two strains of mice: C57BL/6J and Thy1-YFP mice. Intravitreal injections of Norrin or vehicle were done after five days of exposure to 75% oxygen from ages P7 to P12. The C57BL/J mice were followed by Spectral-Domain Optical Coherence Tomography (SD-OCT), and the average nerve fiber layer (NFL) and inner-plexiform layer (IPL) thicknesses were measured at twenty-four locations per retina at P42. Additionally, some C57BL/J retinas were flat mounted and immunostained for the RGC marker, Brn3a, to compare the population density of surviving retinal ganglion cells. Using homozygous Thy1-YFP mice, single intrinsically fluorescent RGCs were imaged in live animals with a Micron-III imaging system at ages P21, 28 and P42. The relative percentage of YFP-fluorescent RGCs with dendritic arbors were compared. At age P42, the NFL was thicker in Norrin-injected OIR eyes, 14.4 μm, compared to Vehicle-injected OIR eyes, 13.3 μm (p = 0.01). In the superior retina, the average thickness of the IPL was greater in Norrin-injected OIR eyes, 37.7 μm, compared to Vehicle-injected OIR eyes, 34.6 μm (p = 0.04). Retinas from Norrin injected OIR mice had significantly more surviving RGCs (p = 0.03) than vehicle-injected mice. Based upon NFL thickness and counts of RGCs, we conclude that Norrin treatment, early in the ischemic phase, increased the relative population density of surviving RGCs in the central retinas of OIR mice.
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http://dx.doi.org/10.1016/j.exer.2017.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669624PMC
November 2017

THE CUTTING EDGE OF RETINOPATHY OF PREMATURITY CARE: Expanding the Boundaries of Diagnosis and Treatment.

Retina 2017 Dec;37(12):2208-2225

Associated Retinal Consultants, Royal Oak, Michigan.

Purpose: To discuss the latest advances and controversies in the diagnosis and care of infants with retinopathy of prematurity (ROP).

Methods: Literature review.

Results: Retinopathy of prematurity remains a major global issue. Industrialized nations now treat profoundly premature infants with posterior and aggressive disease, and middle-income nations are experiencing ROP epidemics. Remote digital imaging may address the decreasing ratio of ROP providers to premature infants, in addition to improving patient care. Widefield angiography, optical coherence tomography, and the Wnt signaling pathway have provided new insights into ROP pathogenesis. Anti-vascular endothelial growth factor treatment is increasing in popularity, but the dearth of information to guide dosing, unpredictable reactivation, persistent vascular abnormalities, the "crunch" phenomenon, and the presently unknown effects of systemic vascular endothelial growth factor suppression remain issues to continue investigating. Neurodevelopmental delay has been raised as a potential consequence, but the evidence currently is weak. Vitrectomy is the treatment of choice for Stages 4 and 5. Illumination techniques, ab interno incisions, plasmin-assisted vitrectomy, staged surgery in the interest of corneal clearing for advanced Stage 5, and immediate sequential bilateral vitreoretinal surgery, are useful techniques.

Conclusion: We are making progress in ROP management. Our goal as clinicians is to continue expanding the boundaries of our abilities to keep this blinding disease in check globally.
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http://dx.doi.org/10.1097/IAE.0000000000001719DOI Listing
December 2017

Wnt signaling pathway in retinal vascularization.

Eye Brain 2016 9;8:141-146. Epub 2016 Aug 9.

Associated Retinal Consultants, Royal Oak, MI, USA.

Wnt-signaling, a ubiquitous pathway that directs differentiation, cell polarity, and tissue specificity, has been implicated as an important gene-expression pathway in retinal development. An increasing body of evidence supports the importance of Wnt-signaling, and specifically, norrin-mediated Wnt-signaling in retinal development and retinal maintenance. Gene mutations affecting the Wnt-signaling pathways result in a variety of inherited vitreoretinopathies. Additionally, there is growing evidence that prematurity and associated retinopathy are associated with alterations in the Wnt-signaling pathways. Further investigations may allow for improved diagnoses, management, and therapies in the future.
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http://dx.doi.org/10.2147/EB.S94452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398754PMC
August 2016

PROGRESSIVE RETINAL DETACHMENT IN INFANTS WITH RETINOPATHY OF PREMATURITY TREATED WITH INTRAVITREAL BEVACIZUMAB OR RANIBIZUMAB.

Retina 2018 Jun;38(6):1079-1083

Associated Retinal Consultants, Royal Oak, Michigan.

Purpose: Fibrovascular contraction and tractional retinal detachment (TRD) are recognized complications associated with the use of anti-vascular endothelial growth factor agents in vasoproliferative vitreoretinopathies. The authors characterize TRDs that developed after intravitreal bevacizumab or ranibizumab therapy for vascularly active retinopathy of prematurity.

Methods: This is an international, multicenter, interventional, retrospective, case series. Thirty-five eyes from 23 infants were included. Inclusion required anti-vascular endothelial growth factor treatment of Type 1 retinopathy of prematurity with progression to TRD.

Results: Mean gestational age was 26 ± 2 weeks, and mean birth weight was 873 ± 341 g. Mean postmenstrual age on the day of injection was 35 ± 2 weeks. Retinal detachment was noted a mean of 70 days (median, 34; range, 4-335) after injection. Eleven percent detached within 1 week, 23% within 2 weeks, and 49% within 4 weeks. The highest stage of retinopathy of prematurity noted was 4A in 29%, 4B in 37%, and 5 in 34% of eyes. Time to RD negatively correlated with postmenstrual age at the time of injection (Rho = -0.54; P < 0.01). Three TRD configurations were observed: 1) conventional peripheral elevated ridge or volcano-shaped Stage 5 detachment, 2) midperipheral detachment with tight circumferential vectors, and 3) very posterior detachment with prepapillary contraction. Full or partial reattachment was achieved with surgical intervention in 86% of eyes.

Conclusion: Progressive atypical TRD may occur after anti-vascular endothelial growth factor injections for retinopathy of prematurity. The configuration of the detachment varies with the extent of primary retinal vascularization present at the time of treatment.
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http://dx.doi.org/10.1097/IAE.0000000000001685DOI Listing
June 2018