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.

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.

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.

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.

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.

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.

Choroidal schwannoma in a 6-month-old girl.

Choroidal schwannomas are exceedingly rare in children, with only 6 cases reported in children younger than 18 years of age and none in those younger than 9 years. We report a 6-month-old infant presenting with a large noncalcified amelanotic mass with secondary glaucoma that mimicked an atypical retinoblastoma, leading to emergent enucleation for therapeutic and diagnostic purposes. Pathology revealed a total retinal detachment, glaucomatous damage, and a large mass arising from the peripapillary posterior choroid with areas of Antoni A pattern and S-100 staining consistent with the diagnosis of an intraocular schwannoma. This is the first intraocular schwannoma described in an infant.

Keloidal scarring in hard palate grafts.

Hard palate grafts are a commonly accepted treatment for lower eyelid retraction and are typically associated with low complication rates. The authors present a case of bilateral keloidal scarring within hard palate grafts requiring surgical excision. A 72-year-old woman who had undergone bilateral hard palate grafts to her lower eyelids for lower eyelid retraction was referred for the evaluation of ocular irritation. She was diagnosed with bilateral hypertrophy of the grafts with secondary entropion. The grafts were excised; the pathology was consistent with keloidal scarring. To the authors' knowledge, there is no previously reported case of bilateral keloidal scarring in normal donor tissue, which required excision of the hard palate grafts. It is important for oculoplastic surgeons to be aware of this potential complication when considering, discussing, and consenting patients for eyelid reconstruction with hard palate grafting.

Uveitis following intravitreal bevacizumab: a non-infectious cluster.

BACKGROUND AND OBJECTIVE: In this retrospective case series, the authors report seven cases of bevacizumab-related uveitis that occurred within a 4-month period. PATIENTS AND METHODS: Seven eyes of six patients developed non-infectious uveitis following bevacizumab intravitreal injections in a cohort of 978 consecutive bevacizumab injections. RESULTS: The mean age of patients was 74.6 years (range: 26 to 92). All patients developed symptom onset within 1 day of injection. Shared signs and symptoms included corneal edema, anterior chamber and vitreous cell, conjunctival injection, ocular pain, and lack of hypopyon. In all patients, visual acuity returned to within one line of baseline acuity. All seven eyes had been previously injected with bevacizumab, with a mean number of antecedent injections of 6.1 (range: 3 to 12). CONCLUSION: A cluster of sterile bevacizumab-related uveitic reactions was described in this case series. Acute onset of symptoms, absence of hypopyon, a predominant anterior segment reaction, and prompt improvement on topical steroid therapy are useful clinical features distinguishing this uveitic syndrome from infectious endophthalmitis.

Diffuse anterior retinoblastoma without retinal involvement.

PURPOSE: To present a unique case of an 8.5-year-old child with unilateral, anterior, pseudouveitis. He was found to have unilateral, invasive, small blue cell tumor of the anterior segment that was diagnosed as diffuse infiltrating retinoblastoma despite lack of retinal involvement on fundus examination or histopathologic analysis. DESIGN: Interventional case report. PARTICIPANTS: One patient. INTERVENTION: The patient was treated with topical prednisolone acetate 1% and oral prednisone with no improvement in anterior chamber reaction. The patient underwent fine-needle aspiration biopsy (FNAB) of anterior chamber fluid, the results of which were consistent with a primitive neuroectodermal neoplasm, either retinoblastoma or medulloepithelioma. Retinoblastoma was favored strongly, and the patient underwent enucleation followed by chemotherapy with vincristine, carboplatin, and etoposide, and radiation to the eye socket of 4140 cGy total was performed. MAIN OUTCOME MEASURES: The patient is alive and tumor free with follow-up of 5 years. RESULTS: Microscopic examination demonstrated cells similar to those seen on the FNAB infiltrating the iris stroma, trabecular meshwork, Schlemm's canal, and the inner portion of sclera in the region of the angle. No calcifications were identified. Serial sections of the entire globe were performed to determine the origin of the tumor. No retinal involvement was identified, and tumor was not seen to arise from the ciliary epithelium. Immunohistochemistry demonstrated positive staining with synaptophysin and negative staining with leukocyte common antigen and CD34. CONCLUSIONS: This patient represents a case of diffuse anterior retinoblastoma with lack of obvious retinal involvement. Morphologic features typical of medulloepithelioma were not found on pathologic analysis. Although the patient lacked a retinal focus, he is alive at 5 years without evidence of recurrence of tumor.

Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness.

Leber's congenital amaurosis (LCA) is a group of severe inherited retinal degenerations that are symptomatic in infancy and lead to total blindness in adulthood. Recent clinical trials using recombinant adeno-associated virus serotype 2 (rAAV2) successfully reversed blindness in patients with LCA caused by RPE65 mutations after one subretinal injection. However, it was unclear whether treatment of the second eye in the same manner would be safe and efficacious, given the potential for a complicating immune response after the first injection. Here, we evaluated the immunological and functional consequences of readministration of rAAV2-hRPE65v2 to the contralateral eye using large animal models. Neither RPE65-mutant (affected; RPE65(-/-)) nor unaffected animals developed antibodies against the transgene product, but all developed neutralizing antibodies against the AAV2 capsid in sera and intraocular fluid after subretinal injection. Cell-mediated immune responses were benign, with only 1 of 10 animals in the study developing a persistent T cell immune response to AAV2, a response that was mediated by CD4(+) T cells. Sequential bilateral injection caused minimal inflammation and improved visual function in affected animals. Thus, subretinal readministration of rAAV2 in animals is safe and effective, even in the setting of preexisting immunity to the vector, a parameter that has been used to exclude patients from gene therapy trials.

Secretory meningiomas of the orbit.

Meningiomas are histologically heterogeneous tumors with at least 15 different subtypes. They can be subdivided into well-differentiated, atypical, and anaplastic or malignant categories. The secretory meningioma is a well-differentiated variant, is relatively rare. Orbital involvement of secretory meningiomas is rarity. We report two cases of secretory meningiomas of orbit and review of current literature.

Donor-related Candida keratitis after Descemet stripping automated endothelial keratoplasty.

PURPOSE: To report 2 cases of donor-to-host transmission of Candida albicans interface keratitis after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: We performed clinical and microbiologic examinations on 2 patients who underwent DSAEK for pseudophakic corneal edema. RESULTS: Two patients underwent uneventful DSAEK surgery using corneal tissue from the same donor. The donor corneoscleral rims were cultured at the time of surgery and both rims subsequently grew C. albicans and Candida glabrata. Approximately 5 weeks after surgery, infiltrates were noted in the DSAEK interface in both of these patients. Despite treatment with antifungal therapy, the Candida keratitis was unable to be controlled medically and required surgical intervention in each case, after which there was no recurrence of infection. CONCLUSIONS: Candida interface keratitis can occur after DSAEK. These 2 cases emphasize the importance of donor corneoscleral rim cultures, especially with the increase in lamellar and endothelial keratoplasty, which can make such interface infections more difficult to diagnose and treat. Patients with fungal positive donor corneal rim cultures should be prophylactically treated with antifungal therapy.