Risk Factors for Fibrous Ingrowth in Eyes Requiring Primary Keratoplasty.

PURPOSE: The aim of this study was to define risks for corneal transplantation associated with fibrous ingrowth among first-time transplant recipients. METHODS: We performed a retrospective case-control study of patients with a histopathologic diagnosis of fibrous ingrowth between 2002 and 2019. Patients with fibrous ingrowth from a first corneal specimen were included. Those with incomplete records were excluded. A 1:2 case-control ratio was used. Controls were matched using surgical indication, surgery year, transplantation method, sex, and age. RESULTS: Seventy-eight eyes (76 patients) were included and matched with 160 control eyes. The incidence of fibrous ingrowth found on a first corneal transplant was 0.6% per year. The most common keratoplasty indications were pseudophakic corneal edema (n = 25, 32%) and aphakic corneal edema (n = 15, 19%). Cases were more likely to have a history of ocular trauma (odds ratio [OR], 2.94; 95% CI, 1.30-6.30; P = 0.007), uveitis (OR, 2.73; 95% CI, 1.12-6.63; P = 0.022), retinal detachment or previous retinal surgery (OR, 2.40; 95% CI, 1.34-4.30; P = 0.003), glaucoma tube-shunt surgery (OR, 2.70; 95% CI, 1.29-5.65; P = 0.007), aphakia (OR, 3.02; 95% CI, 1.61-5.67; P = 0.0004), or iris derangement (OR, 10.52; 95% CI, 5.45-20.30; P <0.0001). A multivariate logistic regression model using iris derangement, history of ocular trauma, history of uveitis, and history of cataract surgery demonstrated 81% sensitivity and 66% specificity in predicting presence of fibrous ingrowth. CONCLUSIONS: A history of ocular trauma, uveitis, retinal detachment or previous retinal surgery, glaucoma tube-shunt surgery, aphakia, and iris derangement are risks for detecting fibrous ingrowth among first-time keratoplasty recipients. Patients with these conditions should be monitored closely for corneal decompensation.

Posterior Embryotoxon Revisited: An Immunohistologic Study.

PURPOSE: This series describes the immunopathologic features of posterior embryotoxon (PE) and demonstrates that it is not an anterior displaced Schwalbe's line as commonly described, but a peripheral corneal stromal nub variable in location with abnormal extracellular matrix. DESIGN: Case series. PARTICIPANTS: Archived specimens from patients with PE. METHODS: Sections from archived formalin-fixed, paraffin-embedded specimens (n = 9; 7 autopsy and 2 trabeculectomy specimens) were examined by light microscopy. Immunohistochemistry was performed on 5 specimens to characterize the extracellular matrix composition of PE. RESULTS: Posterior embryotoxon appeared as nubs of whorled collagen extending from the corneal stroma, lined in some instances, by Descemet membrane. These nubs were located anterior to Schwalbe's line (n = 4), posteriorly (n = 1), partially embedded in the trabecular meshwork (n = 1), or at Schwalbe's line (n = 2). Qualitatively, collagen I labeling of the PE stroma was similar or weaker than the corneal stroma, whereas collagen III staining was focal and slightly more intense compared with the corneal stroma. Lumican and keratan sulfate staining was similar or less intense in PE compared with the corneal stroma. MAIN OUTCOME MEASURES: Identify location of PE and its immunohistochemical features. CONCLUSIONS: In contrast to the widely accepted definition of PE as a prominent, anteriorly displaced Schwalbe line, histologic evidence suggests that it is a direct extension of the corneal stroma with variable locations that may displace the attenuated Descemet membrane when located anterior to or at Schwalbe's line. Immunohistochemical examination revealed that the composition of PE's extracellular matrix was similar to corneal stroma but with some variability in staining intensity.

A direct transcutaneous approach to infraorbital nerve biopsy.

PURPOSE: To describe a novel transcutaneous infraorbital nerve biopsy technique which can be performed to aid in the diagnosis of perineural invasion (PNI) of facial cutaneous squamous cell carcinoma (SCC). METHODS: A single-center retrospective chart review was performed. Patients diagnosed with SCC with PNI via an infraorbital nerve biopsy between February 2019 and February 2020 were included. Data collected consisted of patient demographics, medical history, clinical presentation and exam, histologic and radiographic findings, treatment, and outcomes. RESULTS: Four patients (3 male, 1 female) met inclusion criteria. The mean age at diagnosis was 79.5 years (range 66-85 years). Three of the four patients had a history of facial skin lesions, including actinic keratosis and SCC, involving the nose, cheek, or ear. One patient had no history of cutaneous malignancy. All patients presented with cranial neuropathies, including total V2 hypoesthesia. The most common presenting symptom was facial pain, followed by diplopia, unilateral facial weakness, and hypoesthesia in the V1 and/or V2 distribution. Transcutaneous infraorbital nerve biopsy in all patients revealed squamous cell carcinoma with no biopsy complications. CONCLUSION: Definitive diagnosis of PNI can be challenging but is important to minimize tumor-related morbidity. Infraorbital nerve biopsy can establish this diagnosis, especially in the context of negative or indeterminate imaging findings. This work comprises the first description of a transcutaneous approach to infraorbital nerve biopsy, which is a minimally invasive technique that can be performed in an outpatient procedure suite with limited to no sedation.

Solitary adult orbital myofibroma: Report of a case and review of the literature.

PURPOSE: Myofibromas are benign soft tissue tumors commonly encountered in infancy and childhood. Developing usually within the first two years of life, they can be multicentric and involve deep visceral organs. OBSERVATIONS: We present the rare occurrence of a solitary orbital myofibroma in an adult patient. The clinical, histopathologic and immunohistochemical findings of the tumor are documented. CONCLUSIONS: A comprehensive review of pediatric and adult orbital and periocular involvement by myofibroma is presented. Its characteristic pathologic and molecular findings are reviewed. IMPORTANCE: Myofibromas are uncommon but important tumors that can occur in the head and neck region, including the orbit. Seen more often in children, they can rarely be encountered in adult patients. Diagnosis is possible with a panel of immunostains and molecular analysis can be further confirmatory.

Metastatic Squamous Cell Carcinoma of the Tonsil Mimicking Choroidal Melanoma.

We describe a case of a 53-year-old man with a history of metastatic squamous cell carcinoma of the tonsil who presented with a large, dome-shaped, choroidal mass in the left eye with concern for extra-ocular extension. Standardized echography showed a choroidal mass with low-to-medium internal reflectivity, pockets of very low reflectivity, positive angle kappa, and 1+ vascularity that were concerning for primary choroidal melanoma. Biopsy of the lesion was consistent with metastatic squamous cell carcinoma of the tonsil rather than melanoma. This is only the second reported case of metastatic squamous cell carcinoma to the choroid presenting with a large vascular tumor with echographic characteristics consistent with choroidal melanoma. The unique vascularity present in some cases of squamous cell carcinoma of the tonsil may explain the vascularity and large height of this patient's lesion. Tumor fine-needle aspiration biopsy can play an important role in patients with choroidal lesions in the setting of unusual primary tumors.

Primary ductal adenocarcinoma of the lacrimal gland: A review and report of five cases.

Primary ductal adenocarcinoma (PDA) is a rare epithelial tumor of the lacrimal gland. Herein we report 5 cases and review 29 published cases of PDA of the lacrimal gland. Among these 5 cases, the most common clinical presentation was painless swelling and/or proptosis of their eye. The size of the lesions ranged from 1.6 to 2.5 cm. Histopathologic examination revealed proliferations of ductal or gland-like cells with vesiculated pleomorphic nuclei and prominent nucleoli. Tumor cells stained positive for epithelial and apocrine differentiation markers. Immunohistochemistry for human epidermal growth factor 2 was positive in 2 of the 4 cases. Four of the five patients were alive at the last follow-up visit. One died with bone metastases, which were diagnosed 25 months after exenteration and then survived an additional 51 months. On reviewing of twenty-nine previously published cases of PDA, the mean age of diagnosis was 58 years, with a male predominance (75%). Fifteen patients (54%) had distant metastases, 1 (4%) had local recurrence, and 10 (37%) suffered from a PDA-related death. PDA is a high-grade aggressive epithelial tumor of the lacrimal gland. Although rare, awareness and recognition of this malignancy are important to help determine prognosis and treatment options.

Urinary ß2-microglobulin and disease activity in patients with tubulointerstitial nephritis and uveitis syndrome.

BACKGROUND: Urinary ß2-microglobulin (Uß2M) is elevated in tubulointerstitial nephritis and uveitis (TINU) syndrome and has emerged as an important diagnostic tool. This study aims to determine whether Uß2M correlates with uveitis activity in TINU. METHODS: Retrospective observational case series of nine patients with TINU and ≥ 30 days follow-up. Presenting symptoms, visual acuity, uveitis characteristics, follow-up, Uß2M, serum creatinine (SCr), urinalysis, and renal biopsy results were collected. RESULTS: A correlation between Uß2M and anterior chamber (AC) cell (r = 0.69, 95% CI 0.46-0.84), flare (r = 0.65, 95% CI 0.39-0.81), trended toward a stronger correlation than SCr and AC cell (r = 0.59, 95% CI 0.29-0.79), flare (r = 0.52, 95% CI 0.19-0.75). Uß2M decreased over 1-2 years while SCr returned to normal within a few months. CONCLUSIONS: Uß2M correlate with uveitis activity and trend down over the course of TINU. Uß2M may serve as a useful tool in determining where patients are in their systemic disease course.

Orbital implant exposure after Acanthamoeba panophthalmitis.

PURPOSE: Acanthamoeba is a protozoa that can lead to severe ocular disease and sequelae. Although intraocular Acanthamoeba infection is rare, the following case demonstrates an unusual presentation of recurrent Acanthamoeba infection in a 30 year old contact lens wearing male. OBSERVATIONS: After presenting with recurrent Acanthamoeba keratitis and undergoing various treatments, the patient developed nodular scleritis, which evolved into panophthalmitis, and ultimately, required enucleation. Eight months post-operatively, the patient developed orbital implant exposure secondary to persistent Acanthamoeba infection and underwent removal of the implant and aggressive, systemic treatment involving a multispecialty care team. He then underwent placement of a dermis fat graft and had no signs of persistent infection at the time of last follow-up, which was 24 months after placement of the dermis fat graft. CONCLUSIONS: and Importance: To the authors' knowledge, this is the first known case of Acanthamoeba infection causing orbital implant exposure. Persistent infection should be considered in Acanthamoeba patients who have undergone enucleation and have orbital implant exposure. Better knowledge regarding the pathogenesis and extracorneal complications of this challenging disease may improve patient care and outcomes.

Identification of Herpes Zoster-Associated Temporal Arteritis Among Cases of Giant Cell Arteritis.

PURPOSE: To examine whether herpes zoster antigen (also called varicella-zoster virus antigen) was detectable in temporal artery biopsies taken from individuals with giant cell arteritis (GCA). DESIGN: Retrospective comparative case series. METHODS: Sections of formalin-fixed paraffin-embedded temporal arteries were examined first by hematoxylin-eosin (H&E) staining to establish the diagnosis of GCA. Adjacent sections of the same biopsy were then examined by immunohistochemistry, using 2 different monoclonal antibodies against a major antigen of varicella-zoster virus called gE. Pathologic specimens were obtained from patients cared for at the University of Iowa and Washington University in St. Louis ophthalmology clinics. RESULTS: The study included biopsies from 25 patients with symptoms of GCA as well as positive H&E pathology and 25 patients with symptoms compatible with GCA but negative H&E pathology. Among the GCA-positive group, 3 patients had positive staining for herpes zoster antigen. Among the GCA-negative group, herpes zoster antigen was not detected in any biopsy. In both groups of patients, false-positive staining for herpes zoster antigen was detected in the presence of calcifications in the arteries. False-positive staining was also detected on some extra-arterial skeletal muscle and erythrocytes. CONCLUSION: Herpes zoster antigen was detected in 3 of 25 temporal arteries from patients with biopsy-proven GCA. One of the 3 positive cases was noteworthy because the patient had had herpes zoster ophthalmicus diagnosed 3 weeks before the onset of GCA symptoms. False-positive staining for herpes zoster antigen was detected on several temporal artery biopsies.

Histochemical Analysis of Glaucoma Caused by a Myocilin Mutation in a Human Donor Eye.

Objective: Mutations in myocilin (MYOC) may cause either juvenile open angle glaucoma (JOAG) or adult-onset primary open angle glaucoma (POAG). MYOC encodes a glycoprotein that is normally secreted from trabecular meshwork cells that regulate intraocular pressure. Prior in vitro, transgenic rodent, and organ culture experiments have suggested that abnormal accumulation of MYOC protein within trabecular meshwork cells is a key step in glaucoma pathophysiology. We investigated the pathogenesis of MYOC glaucoma by examining a donor eye from a patient with JOAG caused by a Tyr437His MYOC mutation. Design: Case-control, immunohistochemical study of a donor eye from a patient with JOAG caused by a Tyr437His MYOC mutation and age-matched control donor eyes. Subjects: An eye from a 59-year-old male with JOAG caused by a Tyr437His MYOC mutation and eyes from five donors (ages 51-66) with no known ocular disease were examined. Methods: Frozen fixed sections of the iridocorneal angle were prepared from the donor eyes of the MYOC glaucoma patient and control eyes. We used antibodies directed against MYOC, collagen IV, and BiP/GRP78 as well as wheat germ agglutinin and concanavalin A lectins to localize MYOC protein in the trabecular meshwork. Main Outcome Measure: Qualitative comparison of MYOC protein labeling and localization in the trabecular meshwork of donor eyes from a glaucoma patient with a MYOC mutation and from control subjects. Results: Using immunohistochemistry, we detected more abundant MYOC protein within the trabecular meshwork of the MYOC glaucoma patient's eye than in control eyes. We further localized MYOC protein within the trabecular meshwork cells of the MYOC glaucoma patient's eye by co-labeling with the endoplasmic reticulum (ER) marker GRP78 (BiP). Little to no MYOC was identified within the trabecular meshwork cells of control eyes. Minimal extracellular MYOC was detected in both MYOC glaucoma eyes and control eyes. Conclusions: This is the first histopathological analysis of an eye from a glaucoma patient with a MYOC mutation. Furthermore, this analysis supports our model of MYOC-associated glaucoma, in which MYOC mutations cause abnormal intracellular retention of MYOC within the ER of trabecular meshwork cells as a key step towards development of glaucoma.

An Analysis of Conjunctival Map Biopsies in Sebaceous Carcinoma.

PURPOSE: To evaluate the need for standardized conjunctival map biopsies in periocular sebaceous carcinoma and to formulate recommendations regarding map biopsy number, location, size, and utility based on analysis of biopsy locations, results, and outcomes. METHODS: Retrospective consecutive series of patients with sebaceous carcinoma treated at a tertiary care hospital from 1988 to 2013. Main outcome measures included conjunctival biopsy locations, number, size, and pathology. RESULTS: A diffuse eyelid pattern was evident on presentation in 28/51 patients (54.9%) versus a solitary eyelid nodule in 23/51 (45.1%). Forty-five patients underwent a total of 429 conjunctival biopsies. The conjunctiva was negative in 277 specimens (64.6%), positive in 121 (28.2%), suspicious in 26 (6.1%), and nondiagnostic in 5 (1.2%). Intraepithelial conjunctival involvement was present in 36 patients (70.6%) of whom 23 (63.9%) presented with a diffuse eyelid appearance. There was no statistically significant correlation between primary tumor location and sites of positive biopsies or biopsy size. The pattern at presentation and location of primary tumor did not correlate with biopsy results. Clinical assessment regarding conjunctival involvement was incorrect in 10 of 23 patients (43.5%) with a solitary nodule. Despite primary tumor resection with clear margins confirmed on pathology, 5 of 45 (11%) patients had locally recurrent sebaceous carcinoma. CONCLUSIONS: Conjunctival biopsy size does not correlate with the presence of tumor in the biopsy. Primary tumor location and pattern of tumor at presentation do not correlate with conjunctival biopsy results. Irrespective of the clinical tumor features, standardized conjunctival map biopsies are essential in staging periocular sebaceous carcinoma.

Immunopathology and histopathology of conjunctival biopsies in patients with presumed idiopathic punctal stenosis.

BACKGROUND/AIMS: Numerous processes have been implicated as causes of punctal stenosis. Recent studies have highlighted inflammation in punctoplasty specimens in patients with punctal stenosis. Conjunctival biopsy has been suggested as a means to determine underlying aetiologies, although little is known regarding what conjunctival pathologies are associated with punctal stenosis. Our objective is to examine the pathological and immunological findings in conjunctival biopsy specimens in patients with presumed idiopathic punctal stenosis. METHODS: A retrospective chart review was performed at a single institution over a 5 year period of patients with presumed idiopathic punctal stenosis who underwent conjunctival biopsy for histopathological and/or direct immunofluorescence (DIF) examination. Patients with known aetiologies of punctal stenosis were excluded. RESULTS: 23 patients met inclusion criteria. Conjunctival biopsies (n=36) from all 23 patients underwent histological examination. 35 specimens (97.2%) showed lymphocytic infiltrates. Two patients (8.7%) had findings suggestive of sarcoidosis. Conjunctival biopsies from 18 of the 23 patients were also evaluated by DIF. Nine patients (50.0%) had fibrinogen characteristics suggestive of lichen planus. There were no complications related to the conjunctival biopsy procedures. CONCLUSIONS: Conjunctiva appears to be an excellent proxy in evaluating patients with presumed idiopathic punctal stenosis. The biopsy is safe and provides ample tissue. Clinically, abnormal tissue should be targeted, if available. 11 of the 23 patients in this study demonstrated findings consistent with underlying immunological disorders, suggesting that conjunctival biopsy may play a role in identifying underlying aetiologies of punctal stenosis. Knowledge of these underlying conditions impacted treatments for several patients.

Ketamine/Xylazine-Induced Corneal Damage in Mice.

PURPOSE: We have observed that the commonly used ketamine/xylazine anesthesia mix can induce a focally severe and permanent corneal opacity. The purpose of this study was to establish the clinical and histological features of this deleterious side effect, its sensitivity with respect to age and anesthesia protocol, and approaches for avoiding it. METHODS: Young C57BL/6J, C57BLKS/J, and SJL/J mice were treated with permutations of anesthesia protocols and compared using slit-lamp exams, optical coherence tomography, histologic analyses, and telemetric measurements of body temperature. RESULTS: Ketamine/xylazine induces corneal damage in mice with a variable frequency. Among 12 experimental cohorts, corneal damage associated with ketamine/xylazine was observed in 9 of them. Despite various treatments to avoid corneal dehydration during anesthesia, the frequency of corneas experiencing damage among responding cohorts was 42% (26% inclusive of all cohorts), which is significantly greater than the natural prevalence (5%). The damage was consistent with band keratopathy. It appeared as a white or gray horizontal band located proximal to the pupil and was positive for subepithelial calcium deposition with von Kossa stain. CONCLUSIONS: The sum of our clinical and histological observations is consistent with ketamine/xylazine-induced band keratopathy in mice. This finding is relevant for mouse studies involving the eye and/or vision-dependent behavioral assays, which would both be prone to artifact without appreciation of the damage caused by ketamine/xylazine anesthesia. Use of yohimbine is suggested as a practical means of avoiding this complication.

Optic Nerve Sheath Fenestration: Current Preferences in Surgical Approach and Biopsy.

PURPOSE: Optic nerve sheath fenestration (ONSF) has evolved since its inception in 1872. Surgical approaches include a lateral orbitotomy, a medial orbitotomy, or a superomedial lid crease. The actual fenestration can be done with slits or a window excision with biopsy. Each variation has its advantages and disadvantages. We describe the current preferences in surgical approach and biopsy for ONSF and examine the value of biopsy in patients who have undergone ONSF. DESIGN: Eight-question survey and retrospective, noncomparative case review. SUBJECTS: All American Society of Ophthalmic Plastic and Reconstructive Surgeons (ASOPRS) members are invited to participate in a survey and ONSFs from 1998 to 2013 at the University of Iowa Hospital and Clinics. METHODS: Data from the survey was analyzed and patient records were reviewed. MAIN OUTCOME MEASURES: Preferred surgical approach, type of fenestration, and biopsy results. RESULTS: Sixty-four percent of responding ASOPRS members (150/236) have not performed an ONSF in the last year. One third of that group has performed an ONSF in the last 5 years. Fifty-nine percent perform a medial; 10%, a lateral and 31%, a superomedial approach. Seventy-three percent perform a window fenestration, and about half of those surgeons send the specimen for pathologic evaluation. Anecdotally, some biopsies from surgeons who were surveyed have revealed new diagnoses. In a chart review of 90 cases of ONSF, no biopsy gave an unexpected result. CONCLUSION: The medial approach for ONSF is most common in our respondents; however, the superomedial lid crease incision is gaining popularity for its efficiency and elegance. Three quarters of surgeons remove a window and a quarter fenestrate with slits. Optic nerve sheath biopsy has limited diagnostic value. In the absence of any evidence to suggest a diagnosis other than idiopathic intracranial hypertension, the usefulness of biopsy during fenestration is low.

Cataract surgery in children with uveitis: retrospective analysis of intraocular lens implantation with anterior optic capture.

PURPOSE: To present experience with cataract extraction in 9 eyes of 7 pediatric patients with chronic uveitis and compare the technique of anterior optic capture in 5 eyes that underwent cataract extraction without optic capture of the intraocular lens (IOL) or were left aphakic. METHODS: A retrospective review of pediatric patients with chronic uveitis undergoing cataract surgery was performed, examining the preoperative and postoperative visual acuity, immunosuppressive therapy, surgical technique, complications, subsequent procedures, and need for escalation of systemic immunosuppressive therapy. The technique of anterior optic capture is described in detail. RESULTS: Of the 9 eyes, 5 underwent cataract extraction with IOL placement with the haptics in the capsular bag and optic prolapsed through the anterior capsulorhexis. One eye underwent cataract extraction with IOL implantation in the bag. Three eyes had lensectomy without IOL placement. The eyes with anterior optic capture had no adverse outcomes and uveitis flares were controlled with topical medications and systemic immunosuppressants; the eye with IOL placement without optic capture had recurrent membranes and uveitis flares, necessitating increased systemic immunosuppression. All eyes achieved best-corrected visual acuity of 20/60 or better by 6 months following surgery and 20/30 or better at the most recent follow-up. CONCLUSIONS: The technique of cataract extraction with IOL placement and anterior prolapse of the optic through the anterior capsulorhexis shows promise to be a safe and viable option for pediatric patients with chronic uveitis treated with systemic immunotherapy.

Examining and processing eye specimens.

This chapter provides basic and useful information about handling and processing eye specimens as well as diagnosing common diseases encountered by ophthalmic pathologists. Each section is devoted to a specific part of the eye (cornea, conjunctiva, iris and cilliary body, choroid, retina, vitreous, and the optic nerve), providing useful pearls about the basic anatomy, disease processes, special staining, and tissue processing.