Publications by authors named "Swarup S Swaminathan"

33 Publications

Rapid initial OCT RNFL thinning is predictive of faster visual field loss during extended follow-up in glaucoma.

Am J Ophthalmol 2021 Mar 25. Epub 2021 Mar 25.

Vision, Imaging & Performance (VIP) Laboratory, Duke Eye Center, Duke University, Durham, NC. Electronic address:

Purpose: To investigate the relationship between the rate of retinal nerve fiber layer (RNFL) loss during initial follow-up and the magnitude of associated visual field loss during an extended follow-up period.

Design: Retrospective cohort study.

Methods: A total of 1,150 eyes of 839 glaucoma patients extracted from the Duke Glaucoma Registry. Rates of RNFL loss were obtained from global RNFL thickness values of the first 5 optical coherence tomography (OCT) scans. Rates of visual field loss were assessed using standard automated perimetry mean deviation (SAP MD) during the entire follow-up period. Joint longitudinal mixed effects models were used to estimate rates of change. Eyes were categorized as fast, moderate or slow progressors based on rates of RNFL loss, with cutoffs of ≤-2 µm/year, -2 to -1 µm/year and ≥-1 µm/year, respectively. Univariable and multivariable regressions were completed to identify significant predictors of SAP MD loss.

Results: The rate of RNFL change was -0.76±0.85 µm/y during initial follow-up, which occurred over 3.7±1.5 years. 765 (66%) eyes were slow, 328 (29%) moderate, and 57 (5%) fast progressors, with rates of RNFL thinning of -0.36±0.54 µm/year, -1.34±0.25 µm/year, and -2.87±1.39 µm/year respectively. The rates of SAP MD loss among slow, moderate, and fast OCT progressors were -0.16±0.35 dB/y, -0.32±0.43 dB/y, and -0.71±0.65 dB/y respectively over the extended follow-up period of 6.1±1.9 years (P<0.001). Age, OCT progressor group, and concurrent SAP rate were all significantly associated with the overall rate of SAP MD loss in a multivariable model (all P<0.001).

Conclusion: Rapid RNFL thinning during an initial follow-up period was predictive of concurrent and subsequent rates of visual field decline over an extended period.
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http://dx.doi.org/10.1016/j.ajo.2021.03.019DOI Listing
March 2021

Widefield optical coherence tomography monitoring of the peri-venular fern-like pattern of paracentral acute middle maculopathy.

Am J Ophthalmol Case Rep 2021 Jun 10;22:101047. Epub 2021 Mar 10.

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

Purpose: To demonstrate the ability of widefield swept source optical coherence tomography (OCT) imaging to monitor peri-venular fern-like patterns of paracentral acute middle maculopathy (PAMM) associated with retinal arterial occlusions.

Observations: The peri-venular fern-like pattern of PAMM was diagnosed on the 12 × 12 mm structural OCT images from three patients. Fluorescein angiography images were unremarkable. Over time, all three patients demonstrated significant improvement in visual acuity with resolution of their peri-venular PAMM.

Conclusions: The peri-venular fern-like pattern of PAMM is usually associated with retinal vein occlusions, but we identified three cases with this pattern in eyes with presumed incomplete retinal arterial occlusions. Our cases support the ischemic cascade theory that begins within the deep capillary plexus and ascends in the retina depending on the severity of the ischemic event. Using the 12 × 12 mm structural OCT images, we are able to demonstrate a wider area of ischemia in PAMM compared with the traditional 6 × 6 mm scans.
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http://dx.doi.org/10.1016/j.ajoc.2021.101047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973291PMC
June 2021

Effect of Intravitreal Injections on Retinal Imaging Metrics in Glaucomatous and Non-Glaucomatous Eyes.

Curr Ophthalmol Rep 2020 Sep 4;8(3):111-119. Epub 2020 Jun 4.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

Purpose Of Review: To summarize the available literature on retinal imaging metrics in the context of intravitreal injections in glaucomatous and non-glaucomatous eyes.

Recent Findings: The retinal nerve fiber layer (RNFL) in injected non-glaucomatous eyes appears to thin at a similar rate to uninjected fellow eyes. A total of four studies evaluating RNFL thinning in injected glaucomatous eyes yielded mixed results, with more recent longitudinal investigations suggesting a potential association. The ganglion cell-inner plexiform layer is also being studied as a potential endpoint in both glaucomatous and non-glaucomatous eyes following intravitreal injections.
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http://dx.doi.org/10.1007/s40135-020-00235-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962983PMC
September 2020

Artificial intelligence and complex statistical modeling in glaucoma diagnosis and management.

Curr Opin Ophthalmol 2021 Mar;32(2):105-117

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

Purpose Of Review: The field of artificial intelligence has grown exponentially in recent years with new technology, methods, and applications emerging at a rapid rate. Many of these advancements have been used to improve the diagnosis and management of glaucoma. We aim to provide an overview of recent publications regarding the use of artificial intelligence to enhance the detection and treatment of glaucoma.

Recent Findings: Machine learning classifiers and deep learning algorithms have been developed to autonomously detect early structural and functional changes of glaucoma using different imaging and testing modalities such as fundus photography, optical coherence tomography, and standard automated perimetry. Artificial intelligence has also been used to further delineate structure-function correlation in glaucoma. Additional 'structure-structure' predictions have been successfully estimated. Other machine learning techniques utilizing complex statistical modeling have been used to detect glaucoma progression, as well as to predict future progression. Although not yet approved for clinical use, these artificial intelligence techniques have the potential to significantly improve glaucoma diagnosis and management.

Summary: Rapidly emerging artificial intelligence algorithms have been used for the detection and management of glaucoma. These algorithms may aid the clinician in caring for patients with this complex disease. Further validation is required prior to employing these techniques widely in clinical practice.
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http://dx.doi.org/10.1097/ICU.0000000000000741DOI Listing
March 2021

Rates of RNFL Thinning in Patients with Suspected or Confirmed Glaucoma Receiving Unilateral Intravitreal Injections for Exudative AMD.

Am J Ophthalmol 2020 Dec 24;226:206-216. Epub 2020 Dec 24.

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

Purpose: This study evaluated whether the rate of retinal nerve fiber layer (RNFL) thinning is faster in eyes receiving intravitreal injections than in fellow uninjected eyes among patients suspected of having or confirmed to have glaucoma and exudative age-related macular degeneration (AMD).

Design: Retrospective comparative cohort study.

Methods: Patients with a diagnosis of unilateral exudative AMD and confirmed to have or suspected of having glaucoma in both eyes receiving unilateral intravitreal injections were identified. Those with ≥3 RNFL optical coherence tomography scans and ≥6 injections were included in the study. Rates of RNFL thinning in the injected eye versus the uninjected eye were estimated using linear mixed models. The main outcome measurement was the differences in rates of RNFL thinning in the injected versus the fellow uninjected eye. The effects of postinjection elevation of intraocular pressure (IOP), injection frequency, and number of injections were also evaluated.

Results: A total of 53 patients met the inclusion criteria, receiving 26.4 ± 15.9 intravitreal injections. The average rate of RNFL thinning in uninjected eyes was -0.620 μm/year (P = .029). Injected eyes had an additional incremental loss of -0.385 μm/year, but this value was not statistically significant (95% confidence interval [CI]: -1.147 to 0.379 μm/year; P = .324). Subgroup analysis with only glaucoma patients (n = 33) also demonstrated a nonsignificant effect of injections (-0.568 μm/year; 95% CI: -1.454 to 0.319 μm/year; P = .212). Postinjection IOP elevation, injection frequency, and total number of injections were not associated with faster RNFL loss.

Conclusions: Among exudative AMD patients with glaucoma or suspected of having glaucoma, the rate of RNFL thinning in eyes receiving intravitreal injections did not significantly differ from that of fellow uninjected eyes.
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http://dx.doi.org/10.1016/j.ajo.2020.12.016DOI Listing
December 2020

Dose-Response Relationship between Intravitreal Injections and Retinal Nerve Fiber Layer Thinning in Age-Related Macular Degeneration.

Ophthalmol Retina 2020 Oct 10. Epub 2020 Oct 10.

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

Purpose: To determine if multiple intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors for unilateral exudative age-related macular degeneration (eAMD) are associated with thinning of the retinal nerve fiber layer (RNFL), we compared RNFL thickness measurements from the injected eye with that of the fellow eye with nonexudative age-related macular degeneration (neAMD).

Design: Retrospective, cross-sectional study.

Participants: Patients undergoing anti-VEGF therapy for unilateral eAMD.

Methods: Patients receiving anti-VEGF therapy secondary to eAMD in 1 eye with neAMD in their fellow eye were identified. Patients with a known diagnosis of glaucoma were excluded. Spectral domain OCT measurements of the peripapillary RNFL thickness from both eyes were performed and compared. The differences in the RNFL thickness measurements between eyes were correlated with the number of injections and the duration of therapy.

Main Outcome Measures: Correlation between the number of anti-VEGF injections and peripapillary RNFL thinning.

Results: A total of 108 eyes of 54 patients were evaluated in this study. The average peripapillary RNFL thickness measurements of the injected eye and fellow eye were 87.3 ± 9.6 μm and 89.0 ± 7.5 μm, respectively (P = 0.055). The RNFL thickness difference (fellow eye minus injected eye) was significantly correlated with the number of injections (r = 0.40, P = 0.002) and months of injections (r = 0.38, P = 0.005). The relationship between the difference in the RNFL thickness and the number of injections had a nonlinear dose-response relationship that became apparent after approximately 30 injections and 50 months of injections.

Conclusions: The difference in RNFL thickness measurements between injected eyes and uninjected fellow eyes was largely within the reported normal limits for interocular differences between healthy eyes. Nevertheless, there was a dose-response relationship between RNFL thinning and number of injections among patients receiving a greater number of injections, suggesting that anti-VEGF injections may have a modest effect on the RNFL thickness after several years of therapy in eyes requiring more anti-VEGF injections; however, we cannot exclude that the RNFL thinning may be secondary to active age-related macular degeneration (AMD) disease progression in both eyes.
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http://dx.doi.org/10.1016/j.oret.2020.10.004DOI Listing
October 2020

Effect of Nylon Wick Technique on Early Intraocular Pressure Control in Nonvalved Aqueous Shunt Surgery.

J Glaucoma 2021 Jan;30(1):32-36

Duke Eye Center, Duke University, Durham, NC.

Precis: The use of nylon wicks with fenestrations in nonvalved aqueous shunt surgery significantly reduces intraocular pressure (IOP) and glaucoma medication usage in the immediate postoperative period compared with the use of fenestrations alone.

Purpose: To compare early postoperative IOP and medication usage in patients undergoing implantation of a nonvalved aqueous shunt device with fenestrations only or fenestrations with nylon wicks.

Methods: A retrospective review of all nonvalved aqueous shunt insertions completed by one surgeon (L.W.H.) was completed using current procedure terminology. Patients undergoing Baerveldt or ClearPath 350 mm2 aqueous shunt insertion with fenestrations only (n=37) or fenestrations with 2 nylon wicks were identified (n=92). All devices were ligated with 7-0 Vicryl (polyglactin) suture, and either 4 fenestrations or 2 fenestrations and two 9-0 nylon wicks were placed anterior to the ligature. Data regarding visual acuity (VA), IOP, number of glaucoma medications, and complications were collected from the preoperative visit just before surgery, postoperative day 1, week 3 (POW3), week 5, and month 2 (POM2). The main outcome measures were VA, IOP, number of glaucoma medications, and complications at all postoperative time points.

Results: There was no difference in logMAR VA between the 2 groups at any time point. At POW3, IOP was significantly lower in the wick group (14.6±7.7 vs. 18.1±8.7 mm Hg, P=0.03). Number of glaucoma medications used was significantly reduced in the wick group at POW3 (0.5±0.9 vs. 1.0±1.2, P=0.02) and POM2 (0.7±1.0 vs. 1.4±1.3, P=0.02). There was no significant increase in the overall rate of complications in the wick group, but there was a higher rate of transient hyphema (28% vs. 8%, P=0.02).

Conclusions: The use of 2 nylon wicks with fenestrations in nonvalved aqueous shunt device implantation can significantly lower IOP and medication burden while awaiting the dissolution of the ligature suture.
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http://dx.doi.org/10.1097/IJG.0000000000001674DOI Listing
January 2021

Progressive Vision Loss in a 62-Year-Old Woman.

JAMA Ophthalmol 2020 Sep 10. Epub 2020 Sep 10.

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

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http://dx.doi.org/10.1001/jamaophthalmol.2020.1746DOI Listing
September 2020

Repair of Rhegmatogenous Retinal Detachment Following Globe Perforation by Retrobulbar Anesthesia.

Ophthalmic Surg Lasers Imaging Retina 2020 04;51(4):249-251

Globe perforation following retrobulbar or peribulbar anesthetic injection is a rare but dreaded complication that often results in suboptimal visual outcomes. This video describes a 72-year-old woman who sustained a globe perforation during retrobulbar block in the setting of cataract extraction and later developed a retinal detachment. The retina was repaired with pars plana vitrectomy and silicone oil, resulting in a favorable visual outcome. The authors discuss various modes of local anesthesia for vitreoretinal surgery, risks for globe perforations, and how to approach retinal detachment secondary to needle perforations, which are complex cases at high risk for proliferative vitreoretinopathy.
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http://dx.doi.org/10.3928/23258160-20200326-08DOI Listing
April 2020

Visual Field Outcomes in the Tube Versus Trabeculectomy Study.

Ophthalmology 2020 09 4;127(9):1162-1169. Epub 2020 Mar 4.

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. Electronic address:

Purpose: To describe visual field (VF) outcomes in the Tube Versus Trabeculectomy (TVT) Study.

Design: Cohort analysis of patients in a multicenter randomized clinical trial.

Participants: A total of 122 eyes of 122 patients, with 61 eyes in both the tube shunt and trabeculectomy groups.

Methods: The TVT Study is a multicenter randomized clinical trial comparing the safety and efficacy of tube shunt surgery (350-mm Baerveldt implant) and trabeculectomy with mitomycin C (MMC) (0.4 mg/ml for 4 minutes) in patients with previous cataract or glaucoma surgery. Enrolled patients underwent perimetry at baseline and annual follow-up visits. The VFs were included if the false-positive rate was ≤20% and false-negative rate was ≤35%. The VFs were excluded if visual acuity <20/400 or loss of ≥2 Snellen lines from baseline was attributed to an etiology other than glaucoma. Longitudinal linear mixed-effects models with best linear unbiased predictions (BLUPs) were applied to estimate rates of change in mean deviation (MD) for each treatment group.

Main Outcome Measure: Rate of MD change during follow-up period.

Results: A total of 436 reliable VFs were analyzed, with an average of 3.6 VFs per eye. Baseline MD was -13.07 ± 8.4 decibels (dB) in the tube shunt group and -13.18 ± 8.2 dB in the trabeculectomy group (P = 0.99). The rate of change in MD was -0.60 dB/year in the tube group and -0.38 dB/year in the trabeculectomy group (P = 0.34). The 95% confidence intervals for the rates of MD change were -0.77 to -0.44 dB/year in the tube group and -0.56 to -0.20 dB/year in the trabeculectomy group. No significant difference in MD slope was seen when patients were categorized by percentage of visits with intraocular pressure (IOP) <18 mmHg or by average IOP. Univariable and multivariable risk factor analyses identified history of diabetes, elevated IOP, and worse MD as baseline factors associated with more rapid VF loss.

Conclusions: Slow rates of VF loss were observed after randomized surgical treatment in the TVT Study, but no significant difference in the rate of VF loss was seen after tube shunt implantation and trabeculectomy with MMC. Patients with diabetes, higher IOP, and more severe VF loss at baseline were at higher risk for VF progression.
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http://dx.doi.org/10.1016/j.ophtha.2020.02.034DOI Listing
September 2020

Multimodal Imaging of Punctate Outer Retinal Toxoplasmosis.

Ophthalmic Surg Lasers Imaging Retina 2019 05;50(5):281-287

Background And Objective: To describe the multimodal imaging characteristics associated with punctate outer retinal toxoplasmosis (PORT).

Patients And Methods: Multicenter, retrospective, observational case series of three patients who presented with PORT. Multimodal imaging was reviewed including optical coherence tomography (OCT), fundus autofluorescence, optical coherence tomography angiography, and conventional dye-based angiography.

Results: Patient ages ranged from 13 years to 55 years. Each patient had multiple white, punctate outer retinal lesions in the affected eye at initial diagnosis. OCT showed both inner and outer retinal changes, including disruption of the ellipsoid and interdigitation zones and retinal pigment epithelium/Bruch's membrane complex, as well as punctate, preretinal, hyperreflective lesions at the vitreoretinal interface, which regressed with treatment.

Conclusion: Multimodal imaging is useful in diagnosing and monitoring treatment response in PORT, an uncommon presentation of ocular toxoplasmosis that must be differentiated from white dot syndromes or other causes of unilateral retinitis. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:281-287.].
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http://dx.doi.org/10.3928/23258160-20190503-04DOI Listing
May 2019

Acute Angle Closure Glaucoma in Von Hippel-Lindau Syndrome.

Ophthalmology 2019 05;126(5):691

Department of Ophthalmology, Duke Eye Center, Duke University, Durham North Carolina.

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http://dx.doi.org/10.1016/j.ophtha.2019.02.009DOI Listing
May 2019

Predictors of Neovascular Glaucoma in Central Retinal Vein Occlusion.

Am J Ophthalmol 2019 08 9;204:62-69. Epub 2019 Mar 9.

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

Purpose: To determine the risk factors for development of neovascular glaucoma (NVG) in patients after an acute central retinal vein occlusion (CRVO).

Design: Retrospective cohort study.

Methods: Review of medical records of 646 patients with a diagnosis of CRVO between 2013 and 2017 at the Bascom Palmer Eye Institute.

Inclusion Criteria: (1) CRVO onset to presentation <90 days; (2) absence of anterior segment neovascularization on presentation; (3) no intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection before presentation. Patients meeting inclusion criteria were screened for potential risk factors for development of NVG. Risk of developing NVG was assessed with Kaplan-Meier survival analysis and Cox proportional hazards models.

Results: Thirteen of 98 patients (13%) who met inclusion criteria developed NVG. The mean adjusted time to NVG diagnosis from onset of CRVO-related symptoms was 212 days. Patients presenting with a worse initial visual acuity (P = .034), a relative afferent pupillary defect (RAPD) (P = .002), or a history of systemic hypertension (P = .026) had an increased risk of NVG compared to those who did not. Age, body mass index, history of glaucoma, history of diabetes, and central retinal thickness were not significantly associated with development of NVG.

Conclusions: Risk factors for NVG development included history of systemic hypertension, worse visual acuity on presentation, and RAPD on presentation. Patients presenting with these findings should be followed at closer intervals and informed of the greater risk for neovascularization. Intravitreal anti-VEGF therapy delayed but did not prevent NVG.
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http://dx.doi.org/10.1016/j.ajo.2019.02.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642681PMC
August 2019

Concurrent acute retinal necrosis and orbital inflammation: Report of 2 cases.

Am J Ophthalmol Case Rep 2019 Jun 13;14:47-50. Epub 2019 Feb 13.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

Purpose: To describe the rare entity of concurrent herpetic acute retinal necrosis (ARN) and orbital inflammation.

Observations: Two cases of ARN with simultaneous orbital inflammation are described. A 40-year old male presented with a painful left eye and hand motion visual acuity (VA). Both panuveitis and orbital inflammation with involvement of the sclera and optic nerve were observed. He was initially treated with oral steroid therapy, after which the orbital inflammation improved but the panuveitis remained. A diagnostic anterior chamber paracentesis was positive for HSV-2 by PCR. He was started on systemic antivirals, but ultimately developed a retinal detachment. The second patient was an 18-year old female with hand motion VA in the left eye. Panuveitis and severe conjunctival chemosis were observed. MRI demonstrated dacryoadenitis with preseptal inflammation. The patient was initially started on oral steroid therapy, which alleviated the orbital inflammation but not the intraocular inflammation. An anterior chamber diagnostic paracentesis was positive for HSV-1, after which the patient underwent vitrectomy for a retinal detachment. The patient was started on systemic antiviral therapy.

Conclusions And Importance: Herpetic disease should remain on the differential for cases of concurrent intraocular and orbital inflammation. Early recognition of this process may help prevent severe vision loss. It is important to recognize that orbital inflammation secondary to herpetic disease may be diverse in its presentation.
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http://dx.doi.org/10.1016/j.ajoc.2019.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393694PMC
June 2019

Histologic Analysis of Trabecular Meshwork Obtained From Kahook Dual Blade Goniotomy.

Am J Ophthalmol 2018 08 5;192:198-205. Epub 2018 Jun 5.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA; Miami Veterans Affairs Healthcare System, Miami, Florida, USA. Electronic address:

Purpose: To determine whether there are identifiable, reproducible findings in the trabecular meshwork (TM) of patients with primary open-angle glaucoma (POAG) who underwent Kahook Dual Blade (KDB) goniotomy.

Design: Noncomparative retrospective case series.

Methods: Tertiary academic referral center, Veterans Affairs Medical Center. Thirteen patients (14 eyes) with POAG (100%) were treated with KDB goniotomy from May to December 2017. Isolated TM tissue was collected from 9 patients (10 eyes) and submitted for histologic analysis. Hematoxylin-eosin, periodic acid-Schiff, and elastin Van Gieson stains were completed, in addition to immunohistochemistry for collagen IV.

Results: Mean age of patients was 74.2 ± 6.7 years. Trabecular beams were identified in all 10 specimens, although distorted in 4 samples, of which 3 had a history of laser trabeculoplasty. Collagen IV staining was present in 10 of 10 samples, coating the trabecular beams. Elastin was present in 8 of 10 samples along the trabecular beams. Intraocular pressure and number of glaucoma medications decreased significantly in all cases postoperatively (P < .0001, P = .035, respectively).

Conclusions: This pilot study demonstrates that tissue obtained during KDB goniotomy has a high yield of containing TM compared to reported yield of TM in specimens collected from traditional ab externo trabeculectomy (71% vs 20%, respectively). These goniotomy specimens possess sufficient anatomic preservation to be studied histologically. Trabecular meshwork obtained with this procedure may provide a novel modality to study TM dysfunction in open-angle glaucomas.
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http://dx.doi.org/10.1016/j.ajo.2018.05.028DOI Listing
August 2018

Evolving Indications for Tube Shunt Surgery.

Int Ophthalmol Clin 2018 ;58(3):135-144

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http://dx.doi.org/10.1097/IIO.0000000000000226DOI Listing
February 2019

The Effect of Patient Characteristics and Sleep Quality on Visual Field Performance Reliability.

J Ophthalmol 2018 12;2018:2731260. Epub 2018 Feb 12.

Bascom Palmer Eye Institute, Miami, FL, USA.

Purpose: To investigate the association of automated visual field (VF) reliability indices (false positive [FP], false negative [FN], and fixation loss [FL]) and sleep quality, VF experience, and age.

Methods: Prospective, cross-sectional study. Adult patients (age ≥ 18 years) completing automated VF testing were invited to participate. Baseline participant characteristics were obtained, and all participants were asked to complete the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Nonparametric Spearman correlations and logistical regression models were performed.

Results: 63 patients were enrolled. Lower PSQI score was correlated with higher percentage (%) FL in the right eye ( = 0.03). Fewer prior VF was significantly correlated with higher %FP in the right eye ( = 0.008). Older age was significantly correlated with higher %FN in the left eye ( = 0.01). Greater mean deviation (MD) and pattern standard deviation (PSD) were strongly correlated with higher %FN in the right ( = 0.02 and 0.002, resp.) and left eyes ( = 0.01 and 0.02, resp.).

Conclusion: In this prospective, cross-sectional study, worse MD and PSD are strongly correlated with increased FN in both eyes. Increased FN in the left eye associated with older age might be attributable to test fatigue. Worse sleep quality is associated with decreased FL in the right eye.
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http://dx.doi.org/10.1155/2018/2731260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896407PMC
February 2018

Swept-Source OCT Angiography of Multiple Evanescent White Dot Syndrome With Inflammatory Retinal Pigment Epithelial Detachment.

Ophthalmic Surg Lasers Imaging Retina 2018 02;49(2):145-151

A 30-year-old woman with photopsias and decreased vision was diagnosed with multiple evanescent white dot syndrome (MEWDS) with an atypical inflammatory subfoveal retinal pigment epithelial detachment (PED) and imaged using swept-source optical coherence tomography (SS-OCT) during several visits. SS-OCT imaging revealed a focal area of attenuated choriocapillaris underneath the PED. An attempt to treat the presumed macular inflammatory lesion with corticosteroids resulted in bilateral exudation consistent with central serous chorioretinopathy. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:145-151.].
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http://dx.doi.org/10.3928/23258160-20180129-12DOI Listing
February 2018

Detection of Choriocapillaris Loss in Alport Syndrome With Swept-Source OCT Angiography.

Ophthalmic Surg Lasers Imaging Retina 2018 02;49(2):138-141

A patient previously diagnosed with Alport Syndrome was evaluated using multimodal imaging. Optical coherence tomography (OCT) demonstrated significant thinning of the inner retina within the macula, and inner retinal cysts were found in the peripheral macula. OCT angiography demonstrated loss of the choriocapillaris. Abnormal collagen appears to have multiple deleterious effects on the retinal and choroidal structure and vasculature. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:138-141.].
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http://dx.doi.org/10.3928/23258160-20180129-10DOI Listing
February 2018

Is Obstructive Sleep Apnea Associated With Progressive Glaucomatous Optic Neuropathy?

J Glaucoma 2018 01;27(1):1-6

Department of Ophthalmology, Bascom Palmer Eye Institute.

Purpose: The purpose of this study was to evaluate the relationship between obstructive sleep apnea syndrome (OSAS) and glaucoma progression, and to examine the correlation between OSAS severity and rate of visual field (VF) loss.

Methods: Patients with concurrent diagnoses of open-angle glaucoma and OSAS between 2010 and 2016 were identified. Enrollment criteria consisted of glaucomatous optic neuropathy and VF loss, ≥5 reliable VFs, ≥2 years of follow-up, and polysomnography (PSG) within 12 months of final VF. PSG parameters including apnea-hypopnea index (AHI) and oxygen saturation (SpO2) were collected. Eyes were classified as "progressors" or "nonprogressors" based upon event analysis using Glaucoma Progression Analysis criteria. Two-tailed t test comparisons were performed, and correlations between rates of VF loss and PSG parameters were assessed.

Results: A total of 141 patients with OSAS and glaucoma were identified. Twenty-five patients (age 67.9±7.6 y) with OSAS (8 mild, 8 moderate, 9 severe) were enrolled. Eleven eyes (44%) were classified as progressors, and had more severe baseline VF loss (P=0.03). Progressors and nonprogressors had nonsignificantly different (P>0.05) age (69.9±8.7 vs. 66.4±6.6 y), follow-up (4.4±0.7 vs. 4.3±1.0 y), intraocular pressure (13.1±2.8 vs. 14.9±2.5 mm Hg), mean ocular perfusion pressure (49.7±5.5 vs. 48.8±9.0 mm Hg), AHI (31.3±18.6 vs. 26.4±24.0), body-mass index (27.8±5.5 vs. 28.8±5.6), and SpO2 (94.1±1.6% vs. 94.0±1.6%). AHI was not correlated with slopes of VF mean deviation (r, -0.271; P, 0.190) or pattern standard deviation (r, 0.211; P, 0.312), and no substantial increase in risk of progression was found with increase in AHI.

Conclusions: This study does not support a relationship between OSAS and glaucomatous progression. No correlation was observed between OSAS severity and rate of VF loss.
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http://dx.doi.org/10.1097/IJG.0000000000000837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741474PMC
January 2018

Molecular Characteristics of Conjunctival Melanoma Using Whole-Exome Sequencing.

JAMA Ophthalmol 2017 12;135(12):1434-1437

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

Importance: Conjunctival melanoma (CM) is a highly aggressive ocular cancer for which treatment options are limited; the molecular pathogenesis is poorly understood.

Objective: To identify the molecular characteristics of CM using next-generation whole-exome sequencing (WES).

Design, Setting, And Participants: Whole-exome sequencing was performed on tumor DNA extracted from the archived specimens of 5 patients with CM who had been treated with surgical excision between 2006 and 2011. These samples were analyzed at a tertiary academic ocular oncology referral center using a customized bioinformatic pipeline.

Main Outcomes And Measures: Sample analyses were designed to detect driver mutations, chromosome copy number aberrations, and mutation signatures.

Results: The study’s 5 patients ranged in age from 51 to 77 years. Four of the 5 were female, and all were white. Mutations were detected in known oncogenes, including BRAF, NRAS, NF1, EGFR, ALK, TERT, and APC. None of the mutations associated with uveal melanoma were found. All samples demonstrated a C→T mutation signature typical of UV-induced DNA damage. The most common CNA was a gain in chromosome 6p.

Conclusions And Relevance: In these 5 patients, WES allowed identification of mutations that can be targeted with therapy and supported the role of UV light in CM pathogenesis. These findings indicate a need for larger studies to evaluate the diagnostic, prognostic, and therapeutic value of WES for CM.
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http://dx.doi.org/10.1001/jamaophthalmol.2017.4837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782797PMC
December 2017

Use of Intraoperative Optical Coherence Tomography for Tube Positioning in Glaucoma Surgery.

JAMA Ophthalmol 2017 Dec;135(12):1438-1439

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

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http://dx.doi.org/10.1001/jamaophthalmol.2017.4431DOI Listing
December 2017

Iridoschisis in Angle-Closure Glaucoma Associated With Alkali Burn.

JAMA Ophthalmol 2017 09 14;135(9):e172313. Epub 2017 Sep 14.

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

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http://dx.doi.org/10.1001/jamaophthalmol.2017.2313DOI Listing
September 2017

A Peaked Pupil.

JAMA Ophthalmol 2017 11;135(11):1268-1269

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

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http://dx.doi.org/10.1001/jamaophthalmol.2017.2267DOI Listing
November 2017

Swept-Source OCT Angiography Shows Sparing of the Choriocapillaris in Multiple Evanescent White Dot Syndrome.

Ophthalmic Surg Lasers Imaging Retina 2017 01;48(1):69-74

Two women with unilateral vision loss from multiple evanescent white dot syndrome were imaged serially with swept-source optical coherence tomography (SS-OCT). En face wide-field structural images revealed peripapillary outer photoreceptor disruption better than conventional fundus autofluorescence imaging. OCT angiography (OCTA) imaging showed preservation of flow within the retinal vasculature and choriocapillaris. As OCTA imaging of the choriocapillaris continues to evolve, these images may lay the groundwork for future investigation. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:69-74.].
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http://dx.doi.org/10.3928/23258160-20161219-10DOI Listing
January 2017

Aqueous outflow: segmental and distal flow.

J Cataract Refract Surg 2014 Aug;40(8):1263-72

From Harvard-MIT Division of Health Sciences and Technology (Swaminathan), Harvard Medical School, Boston, Massachusetts, and the Department of Ophthalmology & Visual Sciences (Oh, Kang, Rhee), Case Western Reserve University, Cleveland, Ohio, USA. Electronic address:

Unlabelled: The elevated intraocular pressure (IOP) of primary open-angle glaucoma is caused by impaired outflow of aqueous humor through the trabecular meshwork. Within the juxtacanalicular region, alterations of both extracellular matrix homeostasis and the cellular tone of trabecular meshwork endothelial and the inner wall of Schlemm canal cells affect outflow. Newer pharmacologic agents that target trabecular meshwork and Schlemm canal cell cytoskeleton lower IOP. Aqueous drainage occurs nonhomogenously with greater flow going through certain portions of the TM and less going through other portions-a concept known as segmental flow, which is theoretically the result of outflow being dependent on the presence of discrete pores within Schlemm canal. The limited long-term success of trabecular meshwork bypass surgeries implicates the potential impact of resistance in Schlemm canal itself and collector channels. Additionally, others have observed that outflow occurs preferentially near collector channels. These distal structures may be more important to aqueous outflow than previously believed.

Financial Disclosure: Dr. Rhee is a consultant to Aerie Pharmaceuticals, Alcon Laboratories, Inc., Allegan, Inc., Aquesys, Inc., Glaukos Corp., Ivantis, Inc., Johnson & Johnson, Merck Sharp & Dohme Corp. and Santen, Inc., and has received research funding from Alcon Laboratories, Inc., Merck Sharp & Dohme Corp., and Ivantis, Inc. No other author has a financial or proprietary interest in any material or method mentioned.
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http://dx.doi.org/10.1016/j.jcrs.2014.06.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151118PMC
August 2014

TGF-β2-mediated ocular hypertension is attenuated in SPARC-null mice.

Invest Ophthalmol Vis Sci 2014 Jun 6;55(7):4084-97. Epub 2014 Jun 6.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.

Purpose: Transforming growth factor-β2 (TGF-β2) has been implicated in the pathogenesis of primary open-angle glaucoma through extracellular matrix (ECM) alteration among various mechanisms. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates ECM within the trabecular meshwork (TM), and is highly upregulated by TGF-β2. We hypothesized that, in vivo, SPARC is a critical regulatory node in TGF-β2-mediated ocular hypertension.

Methods: Empty (Ad.empty) or TGF-β2-containing adenovirus (Ad.TGF-β2) was injected intravitreally into C57BL6-SV129 WT and SPARC-null mice. An initial study was performed to identify a stable period for IOP measurement under isoflurane. The IOP was measured before injection and every other day for two weeks using rebound tonometry. Additional mice were euthanized at peak IOP for immunohistochemistry.

Results: The IOP was stable under isoflurane during minutes 5 to 8. The IOP was significantly elevated in Ad.TGF-β2-injected (n = 8) versus Ad.empty-injected WT (n = 8) mice and contralateral uninjected eyes during days 4 to 11 (P < 0.03). The IOPs were not significantly elevated in Ad.TGF-β2-injected versus Ad.empty-injected SPARC-null mice. However, on day 8, the IOP of Ad.TGF-β2-injected SPARC-null eyes was elevated compared to that of contralateral uninjected eyes (P = 0.0385). Immunohistochemistry demonstrated that TGF-β2 stimulated increases in collagen IV, fibronectin, plasminogen activator inhibitor-1 (PAI-1), connective tissue growth factor (CTGF), and SPARC in WT mice, but only PAI-1 and CTGF in SPARC-null mice (P < 0.05).

Conclusions: SPARC is essential to the regulation of TGF-β2-mediated ocular hypertension. Deletion of SPARC significantly attenuates the effects of TGF-β2 by restricting collagen IV and fibronectin expression. These data provide further evidence that SPARC may have an important role in IOP regulation and possibly glaucoma pathogenesis.
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http://dx.doi.org/10.1167/iovs.13-12463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078948PMC
June 2014

Secreted protein acidic and rich in cysteine (SPARC)-null mice exhibit more uniform outflow.

Invest Ophthalmol Vis Sci 2013 Mar 21;54(3):2035-47. Epub 2013 Mar 21.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.

Purpose: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to regulate extracellular matrix (ECM) in many tissues and is highly expressed in trabecular meshwork (TM). SPARC-null mice have a 15% to 20% decrease in intraocular pressure (IOP) compared to wild-type (WT) mice. We hypothesized that mouse aqueous outflow is segmental, and that transgenic deletion of SPARC causes a more uniform pattern that correlates with IOP and TM morphology.

Methods: Eyes of C57BL6-SV129 WT and SPARC-null mice were injected with fluorescent microbeads, which were also passively exposed to freshly enucleated eyes. Confocal and electron microscopy were performed. Percentage effective filtration length (PEFL) was calculated as PEFL = FL/TL × 100%, where TL = total length and FL = filtration length. IOP was measured by rebound tonometry.

Results: Passive microbead affinity for WT and SPARC-null ECM did not differ. Segmental flow was observed in the mouse eye. SPARC-null mice had a 23% decrease in IOP. PEFL increased in SPARC-null (70.61 ± 11.36%) versus WT mice (54.68 ± 9.95%, P < 0.005; n = 11 pairs), and PEFL and IOP were negatively correlated (R(2) = 0.72, n = 10 pairs). Morphologically, TM of high-tracer regions had increased separation between beams compared to low-tracer regions. Collagen fibril diameter decreased in SPARC-null (28.272 nm) versus WT tissue (34.961 nm, P < 0.0005; n = 3 pairs).

Conclusions: Aqueous outflow in mice is segmental. SPARC-null mice demonstrated a more uniform outflow pattern and decreased collagen fibril diameter. Areas of high flow had less compact juxtacanalicular connective tissue ECM, and IOP was inversely correlated with PEFL. Our data show a correlation between morphology, aqueous outflow, and IOP, indicating a modulatory role of SPARC in IOP regulation.
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http://dx.doi.org/10.1167/iovs.12-10950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621502PMC
March 2013