Publications by authors named "Sander R Dubovy"

154 Publications

Endothelial Biopsy for the Diagnosis and Management of Culture-Negative Retrocorneal Fungal Keratitis With the Assistance of Optical Coherence Tomography Imaging.

Cornea 2020 Dec 16;Publish Ahead of Print. Epub 2020 Dec 16.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL; Athens Vision Eye Institute, Cornea Service, Athens, Greece; and 2nd Department of Ophthalmology, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Purpose: To report a case of a culture-negative deep fungal corneal infection that was diagnosed after histopathology of an anterior segment optical coherence tomography-guided endothelial biopsy.

Methods: A 22-year-old woman with history of contact lens wear and concomitant topical steroid use presented with a mid-stromal corneal infiltrate that failed to respond to oral acyclovir and topical fortified antibiotics. Although cornea stains, cultures, and confocal microscopy showed negative results, there was high clinical suspicion for fungal keratitis. After 2 months on topical natamycin, oral voriconazole, and serial intrastromal and intracameral voriconazole injections, the infiltrate enlarged and deepened. Imaging with anterior segment optical coherence tomography revealed that the infection had progressed to an endothelial plaque.

Results: Diagnostic endothelial biopsy was performed in the operating room. Cultures showed again negative results, whereas histopathology of the removed specimen revealed fungal elements. The postoperative edema at the site of the biopsy resolved over the course of 4 weeks, and a posterior stromal scar formed. Serial intrastromal and intracameral voriconazole injections were continued for the first postoperative month. At the 1-year and the 3-year follow-up examinations, the patient's vision was 20/20 without recurrence.

Conclusions: Intraoperative scraping of the endothelial plaque and histopathologic evaluation of the specimen proved to be of utmost importance for definitive diagnosis and resolution of the culture-negative deep fungal infection in this case. This young patient's cornea was retained and vision remains excellent.
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http://dx.doi.org/10.1097/ICO.0000000000002626DOI Listing
December 2020

Clinical Diagnosis and Histopathologic Features of a Synthetic Fiber Granuloma.

J Pediatr Ophthalmol Strabismus 2020 Dec 11;57:e92-e95. Epub 2020 Dec 11.

The authors report a case of a synthetic fiber granuloma to demonstrate the challenges in diagnosing these lesions and to highlight their histopathologic features. This is the first report in the literature to use histopatho-logic and immunofluorescence studies to characterize the subtype and distribution of macrophages in synthetic fiber granuloma. [J Pediatr Ophthalmol Strabismus. 2020;57:e92-e95.].
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http://dx.doi.org/10.3928/01913913-20200915-01DOI Listing
December 2020

Brolucizumab-related retinal vasculitis with exacerbation following ranibizumab retreatment: A clinicopathologic case study.

Am J Ophthalmol Case Rep 2020 Dec 10;20:100989. Epub 2020 Nov 10.

Bascom Palmer Eye Institute, 900 Northwest 17th Street, Miami, FL, USA.

Purpose: To describe the clinical and pathologic characteristics of a case of retinal vasculitis and vitritis following brolucizumab administration and subsequent ranibizumab treatment.

Observations: A 76-year old Caucasian woman experienced pain, decreased vision and floaters one week after receiving her third monthly intravitreal brolucizumab injection in the right eye for exudative age-related macular degeneration. Examination was significant for 0.5+ anterior chamber cells, vitritis, mild peripheral vascular sheathing, and decreased vision from 20/70 to 20/200. She was started on topical 1% prednisolone acetate with improvement in her examination. She was switched to ranibizumab one month after her last brolucizumab injection of the right eye. Three weeks after her ranibizumab injection, she noticed photophobia, pain and decreased vision. Examination revealed worsening uveitis, vitritis, vascular sheathing, and decreased vision to count fingers. Despite starting on 0.05% difluprednate drops every 2 hours and oral high-dose methylprednisolone, the patient did not have any significant improvement in her symptoms or examination. She underwent pars plana vitrectomy and vitreous biopsy with intravitreal triamcinolone injection to the right eye. Vitreous biopsy and culture ruled out infectious endophthalmitis, and further cytopathologic analysis revealed chronic inflammatory infiltrate.

Conclusion And Importance: Treatment with brolucizumab can result in intraocular inflammation and retinal vasculitis likely due to a delayed hypersensitivity reaction to the drug, supported by cytopathologic analysis of a vitreous sample. We demonstrate a case where retreatment with an alternative anti-VEGF agent resulted in worsening vision and vasculitis.
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http://dx.doi.org/10.1016/j.ajoc.2020.100989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695942PMC
December 2020

Clinicopathologic Correlation of Preretinal Tissues in Myopic Traction Maculopathy.

Retina 2020 Nov 20. Epub 2020 Nov 20.

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

Purpose: To evaluate histopathologic features of preretinal tissues (PRTs) removed from eyes with myopic traction maculopathy (MTM).

Methods: We retrospectively studied PRT specimens from eyes with MTM removed during pars plana vitrectomy (PPV). A control group of 6 idiopathic epiretinal membranes (ERMs) was studied for comparison.

Results: Six MTM specimens were studied histopathologically. Outer retinal schisis-like thickening was present in 100% of pre-operative OCT images; 4 of 6 eyes had subfoveal neurosensory retinal detachment. Postoperative OCTs demonstrated complete resolution of the schisis-like appearance in all eyes; a full-thickness macular hole occurred in 2 of 6 eyes. Histopathologic examination disclosed fibrocellular tissue that was strongly positive for glial fibrillary acidic protein (GFAP), weak to moderately positive for cytokeratin (CK), and weakly positive for smooth muscle actin (SMA) and CD68. There were no apparent histopathologic or immunohistochemical differences between PRTs from eyes with MTM and idiopathic ERMs from control eyes.

Conclusion: The outer retinal schisis-like thickening, commonly also associated with subretinal fluid, that characterizes MTM is associated with PRTs that are histopathologically indistinguishable from idiopathic ERMs. These findings suggest that anteroposterior traction caused by axial elongation rather than a uniquely abnormal cellular process is the etiologic mechanism of MTM.
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http://dx.doi.org/10.1097/IAE.0000000000003045DOI Listing
November 2020

Endothelial Cell Loss in Corneal Grafts From Donors Who Sustained Gunshot Wound to the Head or Airbag Deployment in a Motor Vehicle Accident.

Cornea 2020 Oct 21. Epub 2020 Oct 21.

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

Purpose: To compare the endothelial cell density (ECD) and quality of corneal grafts from young donors who sustained airbag deployment in motor vehicle accidents (MVA) or gunshot wounds (GSW) to the head with grafts from donors of similar age who died of other causes.

Methods: This is a retrospective comparative series of 65 corneal grafts from 33 young donors (mean age, 29.60 ± 8.95 yrs), with the cause of death either MVA with airbag deployment (n = 7), GSW to the head (n = 14), or other nontrauma-related cause (n = 12). Donor characteristics, graft quality on slit-lamp examination, ECD, and areas of endothelial cell loss on specular microscopy were compared between the groups.

Results: Donor age, graft quality on slit-lamp examination, and death-to-preservation time were similar between the groups. Statistically significant differences in focal areas of endothelial cell loss were found in the MVA- and GSW-derived grafts compared with the nontrauma-related grafts (85.7% vs. 0%, P value 0.0002 and 92.5% vs. 0%, P value <0.0001, respectively). Mean ECD was significantly lower in the 14 MVA-derived grafts (ECD, 3117 ± 218 cells/mm) and in the 27 GSW-derived grafts (ECD, 3234 ± 381 cells/mm) than in the 24 nontrauma-related grafts (ECD, 3511 ± 312 cells/mm, P values 0.0002 and 0.0068, respectively). No primary graft failures were reported for any of the grafts by masked observers.

Conclusions: MVA- and GSW-derived grafts have lower ECD counts and more areas of endothelial cell loss compared with nontrauma-related grafts. Further studies are needed to evaluate long-term outcomes of such donor grafts.
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http://dx.doi.org/10.1097/ICO.0000000000002563DOI Listing
October 2020

Scleral Erosion Secondary to MIRAgel Scleral Buckle.

Ophthalmic Plast Reconstr Surg 2020 Oct 16. Epub 2020 Oct 16.

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

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http://dx.doi.org/10.1097/IOP.0000000000001875DOI Listing
October 2020

Clinicopathologic correlation of aniridia: Optical coherence tomography angiography and histopathologic observations.

Am J Ophthalmol Case Rep 2020 Dec 11;20:100919. Epub 2020 Sep 11.

Department of Ophthalmology, Duke University, Durham, NC, USA.

Purpose: To describe optical coherence tomography angiography (OCTA) findings in a patient with aniridia and correlate with representative histopathology.

Observations: OCTA images of the macula of a pediatric aniridic patient, who has nystagmus and impaired vision bilaterally, demonstrate a complete absence of the foveal avascular zone (FAZ) in both the superficial and deep vascular complexes (SVC and DVC). In addition, larger superficial blood vessels were found to be abnormally diving from the SVC into the DVC. Similarly, immunofluorescence with confocal microscopy imaging of a retinal histopathology specimen from a 2 month old aniridic patient demonstrated larger vessels diving in the same manner.

Conclusions And Importance: This study highlights the clinical, imaging and histopathologic findings of aniridia. Supine OCTA imaging, performed during examination under anesthesia, allowed for visualization of retinal microvasculature in eyes with nystagmus. The histopathology images helped validate OCTA findings that, with further investigation, may lead to new information about the development of abnormal retinal microvasculature.
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http://dx.doi.org/10.1016/j.ajoc.2020.100919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522690PMC
December 2020

Histopathologic Observations of Eyes in Exenterated Orbits After Neoadjuvant Intra-Arterial Cytoreductive Chemotherapy for Adenoid Cystic Carcinoma of the Lacrimal Gland.

Ophthalmic Plast Reconstr Surg 2020 Aug 25. Epub 2020 Aug 25.

Division of Oculoplastic Surgery, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida.

Purpose: To assess whether exenteration specimens obtained after neoadjuvant intra-arterial cytoreductive chemotherapy (IACC) for adenoid cystic carcinoma of the lacrimal gland demonstrate significant ocular histopathologic alterations that might preclude future pursuit of globe-preserving therapy.

Methods: Retrospective histopathologic analysis of globes in IACC-treated exenteration specimens among the same cohort of patients whose survival outcomes have been reported.

Results: Twenty patients had specimens available. Nineteen globes revealed no abnormalities of the iris, ciliary body, lens, retinal pigment epithelium, choroid, or chorioretinal vasculature. Eighteen globes showed no optic nerve abnormalities. One globe from a patient who refused exenteration until adenoid cystic carcinoma recurrence supervened demonstrated optic nerve edema with a peripapillary hemorrhage and cotton wool spot, as well as hemorrhage and necrosis within an extraocular muscle. Eighteen globes showed no retinal abnormalities attributable to intra-arterial chemotherapy. Three globes showed incidental retinal findings: 2 globes contained 1 to 2 small peripheral retinal hemorrhages and 1 had a pigmented retinal hole. Seven demonstrated mild, chronic extraocular muscle inflammation, and 13 had unremarkable musculature. The single patient who received IACC via the internal carotid rather than the external carotid artery developed ophthalmic artery occlusion with orbital apex syndrome prior to exenteration, and diffuse necrosis and hemorrhage were evident histopathologically.

Conclusions: Neoadjuvant IACC does not cause significant histopathologic damage to key ocular structures or compromise visual function in patients receiving intra-arterial chemotherapy through the external carotid artery. However, delivering chemotherapy through the internal carotid artery may result in visually significant thrombotic vascular events. The generally benign histopathological findings in these exenteration specimens support the concept of IACC delivery through the external carotid system as the cornerstone of a future globe-preserving strategy for lacrimal gland adenoid cystic carcinoma.
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http://dx.doi.org/10.1097/IOP.0000000000001808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904959PMC
August 2020

Clinicopathologic Correlations of Retrocorneal Membranes Associated With Endothelial Corneal Graft Failure.

Am J Ophthalmol 2021 02 15;222:24-33. Epub 2020 Aug 15.

Anne Bates Leach Eye Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA; Florida Lions Ocular Pathology Laboratory, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.

Purpose: To provide clinicopathologic correlations for retrocorneal membranes associated with Descemet stripping automated endothelial keratoplasty (DSAEK) failure.

Design: Retrospective case series.

Methods: The specimens and medical records of the patients diagnosed with clinically significant retrocorneal membranes associated with DSAEK failure at the Bascom Palmer Eye Institute or the University of Miami Veterans Hospital between October 2015 and March 2020 were reviewed for demographics, clinical presentation, comorbidities, and surgeries performed. Histopathologic analysis was performed on hematoxylin-eosin and periodic acid-Schiff sections. Immunohistochemical studies were performed for smooth muscle actin (α-SMA), pancytokeratin, and CK7. Immunofluorescence was performed for vimentin, N-cadherin, ROCK1, RhoA, ZEB1, and Snail.

Results: A total of 7 patients (3 male and 4 female) were identified to have a clinically significant retrocorneal membranes at the time of graft failure. The average age at the time of first DSAEK was 70 years (range: 55-85 years). All patients were pseudophakic and had a glaucoma drainage device in place; 1 had a history of failed DSAEK. Ranging from 0 to 47 months after surgery, a variably thick retrocorneal fibrous membrane was observed, eventually leading to graft failure. Four patients underwent subsequent penetrating keratoplasty and 3 underwent repeat DSAEK. On histopathologic evaluation, a pigmented fibrocellular tissue was identified along the posterior margin of the corneas and DSAEK buttons in all cases. Further characterization with immunohistochemistry and immunofluorescence demonstrated membranes to be negative for pancytokeratin and positive for α-SMA, vimentin, CK7, N-cadherin, ZEB1, Snail, ROCK1, and RhoA.

Conclusions: Fibrocellular retrocorneal membrane proliferation may be associated with DSAEK failure in patients with previous glaucoma drainage device surgery. Our results demonstrate myofibroblastic differentiation and a lack of epithelial differentiation. Positivity for markers of an endothelial-to-mesenchymal transition indicates possible endothelial origin and could be the hallmark for future targeted pharmacotherapy.
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http://dx.doi.org/10.1016/j.ajo.2020.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882638PMC
February 2021

Periorbital Silicone Granulomatosis 30 Years after Acupuncture.

Case Rep Ophthalmol Med 2020 24;2020:6323646. Epub 2020 Jun 24.

Division of Oculofacial Plastic and Reconstructive Surgery, Bascom Palmer Eye Institute, University of Miami-Miller School of Medicine, Miami, FL, USA.

Silicone-based compounds are commonly used in many medical applications, such as coatings for needles and syringes. Foreign body granulomas are a well-recognized complication of silicone exposure; however, they may be challenging to identify without a clear history. A 61-year-old female patient without prior history of periocular injections, filler, or surgery presented to our oculoplastic clinic with multiple periocular lesions. The patient subsequently underwent excisional biopsy of two prominent lesions, which were identified as granulomas on pathology. Further questioning revealed the cause to be facial acupuncture performed decades prior, and a subsequent targeted exam identified additional lesions at other needling sites. A third lesion was subsequently excised, and there was no recurrence at the last follow-up 3 months postsurgery. Acupuncture is an increasingly common but underrecognized source of silicone exposure and can present up to several decades after exposure as a chronic granulomatous response in a characteristic multifocal pattern.
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http://dx.doi.org/10.1155/2020/6323646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334781PMC
June 2020

Akreos AO60 Intraocular Lens Opacification after Retinal Detachment Repair.

Ophthalmol Retina 2020 08 11;4(8):854-856. Epub 2020 Apr 11.

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

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http://dx.doi.org/10.1016/j.oret.2020.03.030DOI Listing
August 2020

A2E Distribution in RPE Granules in Human Eyes.

Molecules 2020 Mar 20;25(6). Epub 2020 Mar 20.

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

A2E (retinylidene-retinylethanolamine) is a major fluorophore in the RPE (retinal pigment epithelium). To identify and characterize A2E-rich RPE lipofuscin, we fractionated RPE granules from human donor eyes into five fractions (F1-F5 in ascending order of density) by discontinuous sucrose density gradient centrifugation. The dry weight of each fraction was measured and A2E was quantified by liquid chromatography/mass spectrometry (LC/MS) using a synthetic A2E homolog as a standard. Autofluorescence emission was characterized by a customer-built spectro-fluorometer system. A significant A2E level was detected in every fraction, and the highest level was found in F1, a low-density fraction that makes up half of the total weight of all RPE granules, contains 67% of all A2E, and emits 75% of projected autofluorescence by all RPE granules. This group of RPE granules, not described previously, is therefore the most abundant RPE lipofuscin granule population. A progressive decrease in autofluorescence was observed from F2 to F4, whereas no autofluorescence emission was detected from the heavily pigmented F5. The identification of a novel and major RPE lipofuscin population could have significant implications in our understanding of A2E and lipofuscin in human RPE.
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http://dx.doi.org/10.3390/molecules25061413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144568PMC
March 2020

Spontaneous regression of ocular surface squamous neoplasia: Possible etiologic mechanisms in cancer resolution.

Ocul Surf 2020 07 10;18(3):351-353. Epub 2020 Mar 10.

Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, FL, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jtos.2020.03.001DOI Listing
July 2020

Anti-Vascular Endothelial Growth Factor Therapy for Choroidal Rupture-Associated Choroidal Neovascularization.

Ophthalmol Retina 2020 02 21;4(2):226-228. Epub 2019 Sep 21.

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

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http://dx.doi.org/10.1016/j.oret.2019.09.008DOI Listing
February 2020

Solitary Fibrous Tumor of the Orbit: A Case Series With Clinicopathologic Correlation and Evaluation of STAT6 as a Diagnostic Marker.

Ophthalmic Plast Reconstr Surg 2020 Mar/Apr;36(2):164-171

Oculofacial Plastic & Reconstructive Surgery, Dean McGee Eye Institute, University of Oklahoma Department of Ophthalmology, Oklahoma City, Oklahoma, U.S.A.

Purpose: To retrospectively describe the clinical characteristics, management, and outcomes of a series of patients with solitary fibrous tumor (SFT) of the orbit and to evaluate signal transducer and activator of transcription 6 (STAT6) as a diagnostic marker.

Methods: Review of a retrospective, noncomparative, consecutive series of patients treated at a single institution with a histopathologic diagnosis of SFT. Demographic, clinical, and imaging data were collected, and paraffin-embedded tissue sections were stained to evaluate for the presence of STAT6 and other pertinent markers.

Results: Twenty-one patients were identified. Most presented with painless progressive proptosis or eyelid swelling for less than 6 months. Imaging revealed well-circumscribed, firm, variably vascular contrast-enhancing lesions with low to medium reflectivity on ultrasound. Four tumors were histopathologically malignant. All tumors were primarily excised, and 1 patient required exenteration. Two patients were treated with adjuvant radiation therapy. Six patients had recurrent disease of which 3 underwent repeat excision, and 2 were observed. No metastatic disease or attributable deaths were observed. All lesions with available tissue stained positively for both CD34 and STAT6.

Conclusion: This is the largest single institution case series of orbital SFT with clinicopathologic correlation and the largest series to confirm the presence of STAT6 in orbital lesions. The management of SFT remains challenging due to unpredictable tumor behavior, and complete excision is the generally recommended treatment. It remains unclear whether a subset of asymptomatic patients with histopathologically benign disease can be durably observed without negative sequelae.
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http://dx.doi.org/10.1097/IOP.0000000000001504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060103PMC
March 2021

Clinicopathologic Correlation of Kaposi Sarcoma Involving the Ocular Adnexa: Immunophenotyping of Diagnostic and Therapeutic Targets.

Ophthalmic Plast Reconstr Surg 2020 Mar/Apr;36(2):185-190

Department of Pathology, Miller School of Medicine, University of Miami, Miami, Florida, U.S.A.

Purpose: To describe the clinicopathologic characteristics and the expression of diagnostic/treatment targets in ocular adnexal Kaposi Sarcoma.

Methods: We conducted a clinical-pathologic retrospective case series. Immunohistochemical staining for cluster of differentiation 31 (CD31), human herpesvirus-8 (HHV8), platelet-derived growth factor receptor alpha (PDGFR-A), vascular endothelial growth factor receptor-1 (VEGF), tyrosine-protein kinase Kit (c-Kit), and programmed cell death protein 1 (PD-1) were performed. Percentage of positive tumor cells was recorded for PD-1; staining intensity and distribution (H-score) were determined for the remaining stains. A Friedman non-parametric ANOVA analysis evaluated the staining.

Results: The study cohort included 13 patients (age 25 to 95 years; mean 46): 7 lesions were in the eyelid, 5 in the conjunctiva, and 1 in the cornea. Nine of 11 lesions (82%) were in human immunodeficiency syndrome-positive patients (human immunodeficiency syndrome status was unknown in 2 cases). Staging included 6 plaques and 7 nodules. The mean H-scores of CD31, HHV8, c-Kit, VEGF, and PDGF-A were 8.00, 8.23, 2.77, 11.54, and 10.31, respectively. Mean PD-1 staining was 6.46%. The Friedman non-parametric ANOVA analysis showed VEGF, PDGF-A, CD31, and HHV8 differed significantly, and all differed significantly from c-Kit. Programmed cell death protein 1 staining was not significant with any clinical variable.

Conclusions: Cluster of differentiation 31 and HHV8 are helpful diagnostic adjuncts for ocular adnexal Kaposi Sarcoma. Platelet-derived growth factor receptor alpha and VEGF are promising treatment targets. Programmed cell death protein 1/PD-L1 and c-Kit are targets that are useful in several tumors; their roles in ocular adnexal Kaposi Sarcoma warrant further studies.
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http://dx.doi.org/10.1097/IOP.0000000000001506DOI Listing
March 2021

Intraocular Metastasis in Unilateral Multifocal Uveal Melanoma Without Melanocytosis or Germline BAP1 Mutations.

JAMA Ophthalmol 2019 Oct 3. Epub 2019 Oct 3.

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

Importance: There has been speculation on the pathogenesis of unilateral multifocal uveal melanoma, but there remains no convincing explanation. Genetic analysis suggests that unilateral multifocal uveal melanoma may represent intraocular metastasis with increased risk of systemic metastasis.

Objective: To evaluate the pathogenesis of unilateral multifocal uveal melanoma.

Design, Setting, And Participants: This clinical case series was conducted in tertiary academic ocular oncology referral centers and included patients with unilateral multifocal uveal melanoma.

Main Outcomes And Measures: Gene expression and mutation profiling of tumor samples.

Results: Four patients (all male; age range, 54-77 years) who were diagnosed with uveal melanoma were treated with plaque brachytherapy, and subsequently developed a second discrete uveal melanoma in the same eye were included. None demonstrated ocular or oculodermal melanocytosis. All 8 tumors available for analysis exhibited class 2 gene expression profiles. In all 4 cases, the initial and subsequent tumors were available for targeted DNA sequencing and identical driver mutations were present in both tumors. Data were collected from September 2015 to August 2018.

Conclusions And Relevance: Unilateral multifocal uveal melanoma in the absence of ocular melanocytosis appears to occur preferentially in tumors with the class 2 gene expression profile and a BRCA1-associated protein 1 gene (BAP1) mutation. The presence of identical BAP1 mutations in multiple tumors in the same eye in the absence of a germline BAP1 mutation suggests intraocular metastasis rather than independent primary tumors. These findings indicate that the first site of metastasis can be within the eye itself and suggest that patients with unilateral multifocal uveal melanoma may be at increased risk of systemic metastasis.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.3941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777244PMC
October 2019

Rose Bengal Photodynamic Antimicrobial Therapy for Patients With Progressive Infectious Keratitis: A Pilot Clinical Study.

Am J Ophthalmol 2019 12 5;208:387-396. Epub 2019 Sep 5.

Anne Bates Leach Eye Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA; Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. Electronic address:

Purpose: To report clinical outcomes of rose bengal photodynamic antimicrobial therapy (RB-PDAT) as an adjunct treatment for severe, progressive infectious keratitis.

Design: Consecutive interventional case series.

Methods: Patients with progressive infectious keratitis unresponsive to standard medical therapy underwent RB-PDAT at the Bascom Palmer Eye Institute from January 2016 through March 2018. RB-PDAT was performed by applying a solution of rose bengal (0.1% or 0.2% RB in balanced salt solution) to the de-epithelialized cornea for 30 minutes, followed by irradiation with a 6 mW/cm custom-made green LED source for 15 minutes (5.4 J/cm).

Results: The current study included 18 patients (7 male and 11 female) ranging from 17 to 83 years old. Acanthamoeba was the most frequent microbe (10/17; 59%), followed by Fusarium spp. (4/17; 24%), Pseudomonas aeruginosa (2/17; 12%), and Curvularia spp. (1/17; 6%); 1 patient had no confirmed microbiologic diagnosis. Main clinical risk factor for keratitis included contact lens wear (79%). The average area of epithelial defect prior to first RB-PDAT was 32 ± 27 mm and average stromal depth hyperreflectivity measured with anterior segment optical coherence tomography was 269 ± 75 μm. Successful RB-PDAT (avoidance of therapeutic keratoplasty) was achieved in 72% of the cases, with an average time to clinical resolution (decreased pain and inflammation with re-epithelialization and infiltrate resolution) of 46.9 ± 26.4 days after RB-PDAT. Time of follow-up after RB-PDAT was 13.3 ± 5.7 months.

Conclusion: RB-PDAT can be considered as an adjunct therapy for cases of severe, progressive infectious keratitis before performing a therapeutic keratoplasty.
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http://dx.doi.org/10.1016/j.ajo.2019.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184264PMC
December 2019

Salzmann nodular degeneration: prevalence, impact, and management strategies.

Clin Ophthalmol 2019 25;13:1305-1314. Epub 2019 Jul 25.

Department of Ophthalmology, University of Miami Miller School of Medicine , Miami, FL 33136, USA.

Purpose: This review will summarize the clinical and histological presentation of Salzmann nodular degeneration (SND), its prevalence and risk factors, potential underlying mechanisms, diagnostic tools, management options, and impact on cataract surgery and co-morbid ocular surface diseases.

Method: PubMed review of 44 articles published between 1976 and 2018.

Results: SND is a corneal disease characterized by whitish gray or bluish nodules on the peripheral or central cornea. The clinical presentation of SND is variable and the nodules can be asymptomatic or cause foreign body sensation and/or blurred vision. Histologically, SND appears as subepithelial nodules with thin overlying epithelium, disrupted or absent Bowman's layer, and activated fibroblasts within the nodule. SND pathogenesis is not fully understood but is thought to involve poor epithelial protection and disruption of the epithelial-stromal interface, allowing for penetration of epithelially derived growth factors into the stroma and subsequent activation of stromal fibroblasts, eventually leading to sub-epithelial deposition of disorganized extracellular membrane components. SND most commonly occurs in Caucasian females in a bimodal distribution, occurring in the fifth or eighth and ninth decades of life. Risk factors for SND include ocular surface diseases and surgery. Surgical intervention is recommended in individuals with symptomatic nodules - primarily superficial keratectomy performed with or without intraoperative mitomycin C, photokeratectomy, and/or amniotic membrane transplantation. These procedures have been successful in removing the lesion and reducing corneal irregularity, but have variable recurrence rates (0-31%).

Conclusion: The pathogenesis of SND is complex and multifactorial. Advances in diagnostic and treatment modalities have allowed for earlier and more accurate diagnosis and effective treatment of SND.
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http://dx.doi.org/10.2147/OPTH.S166280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663077PMC
July 2019

Classification, diagnosis, and management of conjunctival lymphoma.

Eye Vis (Lond) 2019 27;6:22. Epub 2019 Jul 27.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th St., Miami, Miami, FL 33136 USA.

Lymphoma is a malignant lymphoproliferative tumor that can involve the conjunctiva. Approximately 5-15% of all extranodal lymphomas are found in the ocular adnexal region, with approximately 25% of those involving the conjunctiva. Ninety-eight percent of conjunctival lymphomas arise from B-lymphocytes. The most common subtype of conjunctival lymphoma is extranodal marginal zone lymphoma (80%), followed by follicular lymphoma (8%), diffuse large B-cell lymphoma (3%) and mantle cell lymphoma (3%). Natural killer and T cells (NK/T) are rare causes of lymphoma. While most conjunctival lymphomas are localized to the ocular adnexa at the time of presentation, systemic examination and management are of key importance in the long-term care of the patient. This review outlines the classification, etiology, presentation, diagnosis, and management of conjunctival lymphoma. The novel use of high resolution optical coherence tomography, both as a diagnostic tool and as a means for ongoing evaluation during treatment, is illustrated. Treatment options discussed include external beam radiation, chemotherapy, immunotherapy, antibiotic therapy, and combination regimens. Future investigation of the etiology and pathogenesis of conjunctival lymphoma is expected to reveal opportunities for innovative and individualized therapeutic agents. Collaboration between multiple disciplines is key in the advancement of the field.
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http://dx.doi.org/10.1186/s40662-019-0146-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660942PMC
July 2019

Spontaneous regression of conjunctival keratoacanthoma.

BMJ Case Rep 2019 Jul 11;12(7). Epub 2019 Jul 11.

Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA.

An 83-year-old white man presented with a rapidly growing conjunctival mass in his left eye over the course of 1 month. While awaiting surgical intervention, the tumour underwent partial, spontaneous regression to half its original size. The lesion was ultimately excised with wide margins using a no-touch technique and application of cryotherapy to the corneal and conjunctival margins and scleral bed. Histopathological analysis revealed a conjunctival keratoacanthoma. To our knowledge, this is the first case documenting the partial, spontaneous regression of a conjunctival keratoacanthoma over a 5 week time course from the time of diagnosis to surgical excision.
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http://dx.doi.org/10.1136/bcr-2018-228833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626488PMC
July 2019

Ectopic Retinal Pseudocysts: A Clinicopathologic Correlation.

Ophthalmol Retina 2019 07 5;3(7):616-617. Epub 2019 Feb 5.

Department of Ophthalmology, New York University School of Medicine, New York, New York. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2019.01.021DOI Listing
July 2019

The use of high resolution anterior segment optical coherence tomography for the characterization of conjunctival lymphoma, conjunctival amyloidosis and benign reactive lymphoid hyperplasia.

Eye Vis (Lond) 2019 18;6:17. Epub 2019 Jun 18.

1Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136 USA.

Background: Conjunctival lymphoma, conjunctival amyloidosis and benign reactive lymphoid hyperplasia (BRLH) are conditions that often have a similar appearance on the ocular surface. The use of high resolution anterior segment optical coherence tomography (HR-OCT) enables clinicians to evaluate distinctive differences in tissue morphology and cellular patterns in various ocular surface conditions. In this study, we characterize the morphological differences seen in conjunctival lymphoma, conjunctival amyloidosis and BRLH on HR-OCT imaging.

Methods: A retrospective chart review was performed of patients with biopsy proven conjunctival lymphoma, conjunctival amyloidosis and BRLH between 2012 and 2019 at the Bascom Palmer Eye Institute. Patients were excluded if HR-OCT imaging was not performed on initial presentation.

Results: Thirty-four total eyes of 27 patients were identified. Twenty eyes had conjunctival lymphoma (16 patients), 8 eyes had conjunctival amyloidosis (6 patients) and 6 eyes had BRLH (5 patients). All conditions appeared clinically as pink, red or yellow subepithelial lesions but had different features on HR-OCT. In lymphoma, HR-OCT images typically showed homogenous, dark subepithelial lesions with smooth borders, containing monomorphic dot-like infiltrates. HR-OCT images of amyloidosis typically showed heterogeneous, dark lesions with irregular borders, often containing hyperreflective linear infiltrates. HR-OCT images of BRLH showed variable infiltration of the subepithelial tissue, at times with homogenous lesions containing dot-like infiltrates like lymphoma and other times with more hyperreflective, subepithelial tissue. Flow cytometry and gene rearrangement was needed for final differentiation between BRLH and lymphoma lesions.

Conclusions: Distinctive features on HR-OCT of conjunctival lymphoma, conjunctival amyloidosis and BRLH can help characterize these lesions beyond what is apparent with the clinical examination. Future studies can further validate this technology's use with more subtle and challenging lesions.
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http://dx.doi.org/10.1186/s40662-019-0143-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580598PMC
June 2019

Long-term outcomes of riboflavin photodynamic antimicrobial therapy as a treatment for infectious keratitis.

Am J Ophthalmol Case Rep 2019 Sep 1;15:100481. Epub 2019 Jun 1.

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

Purpose: To report the long-term outcomes of three patients with infectious keratitis treated with riboflavin photodynamic antimicrobial therapy (PDAT).

Observations: Case series reporting three patients with infectious keratitis unresponsive to standard medical treatment who underwent riboflavin photodynamic antimicrobial therapy (PDAT) as an adjunct therapy. One male and two female patients were treated, the median age of presentation was 58 years (range, 29-79 years). The organisms isolated and treated were , , and Different risk factors to develop corneal infection ulcers were identified, including corneal abrasion in a contact lens user, history of penetrating keratoplasty with chronic use of topical corticosteroids, and organic trauma. The median follow-up was 47 months (range 37-54 months), and there were no complications secondary to riboflavin PDAT treatment. Two cases underwent optical penetrating keratoplasty after infection was resolved and ocular surface was quiet for at least 3 years.

Conclusions And Importance: Riboflavin PDAT can be used as an adjunct treatment in infectious keratitis to strengthen the corneal collagen fibers, delay keratolysis, and allow more time for antimicrobials to work and this way prevent a corneal perforation.
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http://dx.doi.org/10.1016/j.ajoc.2019.100481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556526PMC
September 2019

Pars plana vitrectomy with intraoperative optical coherence tomography for sub-internal limiting membrane fibrosis excision in a child with Terson syndrome: Surgical and pathological correlation.

Am J Ophthalmol Case Rep 2019 Sep 31;15:100479. Epub 2019 May 31.

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th St, Miami, FL, 33136, USA.

Purpose: To report the intraoperative optical coherence tomography (OCT)-guided surgery of a consolidated sub-internal limiting membrane (ILM) hemorrhage that developed into a sub-ILM fibrotic membrane in a child with a history of Terson syndrome.

Observations: A one year-old boy with a history of Terson syndrome due to a motor vehicle accident presented three months after trauma with a white feather-shaped membrane in the left macula. Preoperative OCT showed a preretinal hyperreflective tissue at the foveal center. The patient underwent pars plana vitrectomy. After separation of the posterior hyaloid, intraoperative OCT did not show any change in structural components. After peeling the ILM, the fibrotic membrane persisted. A bent 30-gauged needle was used to create a plane of dissection in the adherent sub-ILM membrane, which was then peeled with ILM forceps without complication. Post-operative OCT confirmed complete excision without evidence of macular edema. Pathology results indicated presence of fibrocellular tissue that contained hemosiderin, consistent with old organized hemorrhage as a component of the membrane.

Conclusion And Importance: Sub-ILM hemorrhage may persist as a tautly adherent fibrotic membrane that can mimic the appearance of an epiretinal membrane or a chronic subhyaloidal hemorrhage during examination, especially in young children. Intraoperative OCT may aid in select complex macular surgery cases to better delineate the planes of dissection during sub-ILM fibrosis excision.
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http://dx.doi.org/10.1016/j.ajoc.2019.100479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556525PMC
September 2019

Orbital cholesterol granuloma: A report and discussion of orbital findings.

Am J Ophthalmol Case Rep 2019 Sep 21;15:100468. Epub 2019 May 21.

Division of Oculofacial Plastic & Reconstructive Surgery, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, FL, USA.

Purpose: To report a case of orbital cholesterol granuloma and discuss the orbital findings seen in this entity.

Observation: A 38-year-old male presented with an 8-month history of progressive left upper lid ptosis and hypoglobus. Clinical examination was significant for 3 mm of hypoglobus and restricted supraduction in the left eye. Contrasted computed tomography imaging revealed a well-circumscribed lesion in the superotemporal orbit causing extensive bone erosion that appeared to arise from the lacrimal gland. An incisional biopsy was performed, and histopathological evaluation demonstrated fibrovascular tissue surrounding a mixture of histiocytes and cholesterol clefts, consistent with a cholesterol granuloma.

Conclusions And Importance: Orbital cholesterol granulomas are rare lesions that are predominantly found in the superotemporal orbit. These lesions can be associated with marked bony changes in the superotemporal fossa that can be mistaken for a lacrimal gland neoplasm; however, bony erosion is a hallmark of this lesion and should be considered on the differential diagnosis of any lacrimal gland mass with extensive bony erosion.
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http://dx.doi.org/10.1016/j.ajoc.2019.100468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556881PMC
September 2019

Genomic evolution of uveal melanoma arising in ocular melanocytosis.

Cold Spring Harb Mol Case Stud 2019 08 1;5(4). Epub 2019 Aug 1.

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Ocular melanocytosis is the most important predisposing condition for the eye cancer uveal melanoma (UM). Here, we present a patient who developed UM arising within ocular melanocytosis who was treated with enucleation (eye removal), which provided an invaluable opportunity to interrogate both the UM and adjacent uveal tissue containing the melanocytosis using whole-exome and deep-targeted sequencing. This analysis revealed a clonal mutation in the melanocytosis, confirming that this is indeed a neoplastic condition and explaining why it predisposes to UM. This mutation was present in 100% of analyzed UM cells, indicating that a -mutant cell gave rise to the UM. The earliest aberrations specific to the tumor were loss of Chromosomes 1p, 3, and 9p, which were present in virtually all tumor cells. A mutation in arose later on the other copy of Chromosome 3 in a tumor subclone, followed by a gain of Chromosome 8q. These findings provide a mechanistic explanation for the well-known clinical association between ocular melanocytosis and UM by showing that this predisposing condition introduces the first "hit" and thereby increases the stochastic likelihood of acquiring further aberrations leading to UM.
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http://dx.doi.org/10.1101/mcs.a004051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672022PMC
August 2019

Use of High-Resolution Optical Coherence Tomography in the Surgical Management of Ocular Surface Squamous Neoplasia: A Pilot Study.

Am J Ophthalmol 2019 10 1;206:17-31. Epub 2019 Jun 1.

Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA; Florida Lions Ocular Pathology Laboratory, Miami, Florida, USA.

Purpose: To evaluate whether high-resolution optical coherence tomography (HR-OCT) can detect histologic tumor margins of ocular surface squamous neoplasia (OSSN).

Methods: Eight eyes of 8 patients with OSSN undergoing excision were studied prospectively. Immediately before surgery, the tumor was imaged using commercially available HR-OCT to identify the conjunctival margins of the neoplastic lesion. The tumor borders of the lesion determined by HR-OCT were mapped in relation to an anatomic reference point and transferred intraoperatively. The tumor was excised with 4-mm margins from the visible edge of the lesion with a "no-touch" technique. The specimens were sent for pathologic analysis and the histologic tumor margin was compared to the HR-OCT predicted tumor border.

Results: Mean age of the 8 patients was 67 ± 9.9 years. Seven were male, 7 were white, and, ethnically, 3 were Hispanic. All 8 tumors were bulbar and in the exposure zone. Seven tumors were limbal. Corneal extension was present in 5. Mean tumor area was 17.5 ± 11.1 mm. Clinically, 2 of the tumors were leukoplakic, 1 papillomatous, and 3 gelatinous. A conjunctival tumor margin identified with the HR-OCT coincided with the pathologically confirmed margin mark in all eyes.

Conclusions: HR-OCT has the potential to predict histologic tumor margins in OSSN. Optical identification of tumor margins could potentially decrease the incidence of residual positive margins and minimize healthy tissue removal. Advances in HR-OCT technology and integration into a microscope for "real-time" imaging are needed to further improve this technique. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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http://dx.doi.org/10.1016/j.ajo.2019.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885111PMC
October 2019

An Eight-Year-Old Girl Presents With Two Weeks of Vision Loss and Nightly Headaches.

Ophthalmic Surg Lasers Imaging Retina 2019 05;50(5):314-317

Intraocular medulloepithelioma is a rare congenital tumor that arises from the nonpigmented epithelium of the ciliary body. It is the second most common primary intraocular neoplasm during the first decade of life. It may present with an iris mass or cyst (56%), glaucoma (48%), cataract (26%), leukocoria (18%), decrease in vision (41%), or pain (30%). Here, the authors present a case of a medulloepithelioma investigated with multimodal imaging, including the first characterization with intraoperative optic coherence tomography. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:314-317.].
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http://dx.doi.org/10.3928/23258160-20190503-09DOI Listing
May 2019