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Sarcoid-like reaction (SLR) has been reported in patients with solid tumor malignancies, lymphomas, and patients receiving immunotherapy. SLR is often incidentally found during positron emission tomography/computed tomography scans as hilar and/or mediastinal lymphadenopathy. SLR has also been found in the lung, spleen, bone marrow, and skin. Biopsy of these lesions shows noncaseating granulomas. When systemic criteria are not met for sarcoidosis, these noncaseating granulomas are termed SLR. We present the first case in the literature of a case of orbital SLR in a patient with concomitant diffuse large B-cell lymphoma and inverted papilloma of the maxillary sinus. This case highlights the importance of including malignancy in the differential for the presence of a noncaseating granuloma in the orbit.

Competing Interests: The authors report no conflicts of interest.

Competing Interests: The authors report no conflicts of interest.

Background: Excessive daytime sleepiness (EDS) in multiple sclerosis (MS) can be a significant source of disability. Despite this, its prevalence as a patient-reported outcome in this condition has not been well established, and its causes are not well understood., Methods: We prospectively assessed EDS as part of an observational study for patients referred for diagnostic neuro-ophthalmological testing. EDS was evaluated by the Epworth Sleepiness Scale (ESS), and visual data were also collected as part of a research protocol. Analysis with patient data was performed following the exclusion of patients with known primary sleep disorders., Results: A total of 69 patients with MS were included in the analysis. The mean ESS was 6.5 with a SD of 4.3. ESS ≥ 10 was present in 23% of the cohort even in the presence of minimal mean neurological disability (Patient Determined Disease Steps (PDDS) = 1.5). The ESS score was not associated with age, sex, disease-related disability, retinal nerve fiber layer (RNFL), or optic neuritis (ON), but displayed an association with visual dysfunction., Conclusions: There is an increased prevalence of EDS in MS. The increased values of the ESS are not explained by other sleep disorders, suggesting separate mechanisms. Further study of the underlying mechanisms is warranted., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Demyelinating diseases of the central nervous system (CNS) often have neuro-ophthalmological manifestations, and retinal examination can be helpful in making the diagnosis. The latest iteration of optical coherence tomography (OCT)-based criteria for optic neuritis in multiple sclerosis has been developed in the research realm, but its application to clinical practice, and to the more uncommon demyelinating diseases requires further study. The ability to use OCT data to distinguish between various CNS demyelinating disorders could provide additional paraclinical tools to accurately diagnose patients. Furthermore, neuro-ophthalmological testing can define the extent of inflammatory damage in the CNS, independent of patient-reported history. New referrals for OCT at a tertiary multiple sclerosis and neuro-immunology referral centre ( n  = 167) were analysed retrospectively for the self-reporting of optic neuritis, serological test results, and diagnosis. Only approximately 30% of patients with a clinical history of unilateral optic neuritis solely had a unilateral optic neuropathy, nearly 40% of those subjects actually having evidence of bilateral optic neuropathies. Roughly 30% of patients reporting a history of bilateral optic neuritis did not have any evidence of structural disease, with 20% of these patients having a separate, intervenable diagnosis noted on macular scans. OCT is a useful adjunct diagnostic tool in the evaluation of demyelinating disease and has the ability to aid in a more accurate diagnosis for patients. Application of the international interocular difference thresholds to a clinical patient population generally reproduces the original results, emphasising their appropriateness. The analysis distinguishing the demyelinating diseases needs to be replicated in a blinded, multi-centre setting., Competing Interests: Peter Sguigna has no disclosures related to this publication. He has received grant support from the NMSS, CTM, PSTP, and the PRC. He has received consulting fees from Medical Logix LLC, Genentech, and Bristol Myers Squibb. Research reported in this publication was supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001105. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Lauren Tardo has nothing to declare. Kyle Blackburn has nothing to declare. Lindsay Horton has nothing to declare. Darrel Conger has nothing to declare. Robert “Nick” Hogan has nothing to declare. Morgan McCreary has nothing to declare. Benjamin Greenberg has received grant support from the NIH, NMSS, Transverse Myelitis Association, PCORI, Guthy Jackson Charitable Foundation, Chugai, MedImmune, Medday, and Genentech. He has received consulting fees from Alexion, Novartis, EMD Serono, Genentech, and Celgene; he is an unpaid board member of the Transverse Myelitis Association., (© 2022 Taylor & Francis Group, LLC.)

Purpose: To analyze the conjunctival changes, especially goblet cell populations, following Muller's muscle conjunctival resection (MMCR) by histologically evaluating pre and post-MMCR specimens., Methods: This is a retrospective analysis of conjunctival samples sent for histologic evaluation from two patient populations: those who had previously undergone a MMCR and required repeat surgery and controls who underwent a MMCR surgery in a previously unoperated eyelid. Specimens underwent hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining to accentuate goblet cell identification and were evaluated by two ocular pathologists to quantify goblet cell populations and note other anatomical changes. Statistical analysis of goblet cell populations was then performed., Results: Four samples were identified for each group: (1) post-MMCR and (2) control. The mean age was 67 years in the post-MMCR group and 66 years in the control group. The mean goblet cell population was 7 ± 5 cells/mm in the post-MMCR conjunctiva and was 39 ± 16 cells/mm in the control group, which was statistically significant (p = 0.01). Samples from both groups demonstrated scarring and inflammatory cell infiltrate., Conclusions: While there was a relative loss of goblet cell populations in the conjunctiva overlying the region of surgery following MMCR, the lack of dry eye symptoms or changes in tear production reported in prior studies suggests that there may be enough goblet cell population reserve in the remaining accessory lacrimal glands and in the unaltered conjunctiva to provide sufficient lubrication and ocular protection., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Competing Interests: The authors report no conflicts of interest.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

Use of reusable respirators, such as elastomeric half-face respirators (EHFRs), may serve as one solution to combating the problem of N95 respirator shortages experienced during infectious disease emergencies. To clarify whether logistical issues like respirator storage and availability are barriers to implementation of healthcare respiratory protection strategies that include EHFRs, this study aimed to evaluate the availability, storage, and respirator and filter replacement practices of EHFRs used in healthcare settings under routine use. Healthcare workers using EHFRs were surveyed about their use practices. To explore whether issues related to storage and availability of EHFRs affected compliance with assigned respirator use, responses were compared between concordant users and EHFR users who were assigned to use EHFRs but currently use different respirators ("discordant users"). Most concordant EHFR users reported that their respirator was always available when needed (63.8%). Almost two-thirds of concordant but only half of discordant users reported storing their EHFRs conveniently in the patient care area ( p  = <0.001). Among mobile workers, discordant users had higher odds (aOR = 3.2, 95% CI [1.4,7.5]) of reporting that their respirator was not stored in the patient care area, suggesting that storage location has a significant impact on compliance with expected practice, particularly in this group. Storage and access are barriers to optimal elastomeric respirator use in healthcare. Strategies to assure ready availability and storage of respirators will permit EHFR inclusion in pandemic and routine respiratory protection programs.

Foreign-body granuloma formation following filler injections is most commonly seen with permanent fillers; these reactions can occur years following the injections and often require either an intralesional steroid injection or surgical excision. The authors present a case of a 75-year-old woman with a history of systemic sarcoidosis previously treated with numerous immunosuppressive medications who was examined for bilateral infraorbital nodules and swelling that were unresponsive to treatment. She underwent a bilateral anterior orbitotomy through a transconjunctival approach with mass excision. The histologic analysis was consistent with foreign-body granulomata juxtaposed to implantable material, specifically ArteFill, which was injected many years prior. There were no separate noncaseating granulomas to suggest sarcoidosis as the underlying etiology. It is important to consider prior filler injections in patients with sarcoidosis who present with subcutaneous nodules as this changes management and may prevent the need for more aggressive immunosuppressive treatment.

Dermoid cysts in the orbit classically present in children as a mass in the superotemporal or superonasal orbit along the zygomatico-frontal or fronto-ethmoidal suture lines. The presence of a dermoid cyst in the superficial eyelid, not associated with the tarsus, has only been reported once previously. The authors present a case of a 60-year-old man with a painless right lower eyelid mass inferonasally that was completely excised and found to be a dermoid cyst. The presence of a dermoid cyst involving the superficial lower eyelid is very rare. Furthermore, dermoid cysts in adults typically present in the setting of trauma, which was absent in this case. Therefore, it is important to consider dermoid cysts in the differential diagnosis of eyelid lesions in adults.

A 9-month-old male infant with a history of Down syndrome underwent bilateral medial rectus recession. Two weeks postoperatively, he developed leukocoria of the left eye with a white opacity posterior to the lens, numerous undulations, necrosis, and hemorrhages in the retrolental space. His contralateral eye had white retinal lesions nasally. Ultrasound examination of the left eye showed a funnel retinal detachment, loculated debris, and a small, central, hyperechoic area concerning for calcification. He underwent enucleation because retinoblastoma could not be definitively ruled out. Given this patient's low visual potential, enucleation was a definitive and safe treatment option. Ocular pathology showed significant inflammation and necrosis. There was an area of scleral perforation by a suture adherent to the retina and vitreous, surrounded by inflammatory cells. This case uniquely demonstrates pediatric endophthalmitis following strabismus surgery, secondary to scleral perforation confirmed by histopathological analysis. Care must be taken during scleral passage of sutures to prevent inadvertent scleral perforation and the potential complication of endophthalmitis. [J Pediatr Ophthalmol Strabismus. 2017;54:e37-e41.]., (Copyright 2017, SLACK Incorporated.)

Background: Migration of intravitreal silicone to the retrolaminar optic nerve was detected pathologically in 1983, symptomatic migration to the subarachnoid space of the optic nerve was reported in 1994, and asymptomatic intraventricular silicone was first seen radiographically in 1999. Since then, little advance has been made in understanding this phenomenon despite numerous case reports. Although some authors have restricted their attention to cases of intraventricular silicone, we believe that these represent part of a clinical spectrum and that all cases with retrolaminar silicone should be considered. The pathophysiology of silicone migration may have significant implications for the management of patients after vitrectomy., Evidence Acquisition: Two patients were evaluated by the authors. An internet-based literature review was conducted, beginning with the key search terms "intraventricular, intracranial, subarachnoid, or optic nerve silicone," and "complications of vitrectomy or intravitreal silicone." Further searches cascaded from the initial search results. An additional 24 cases of retrolaminar migration of silicone oil were found and summarized. The relevant anatomy and pathophysiology were reviewed, with attention to additional information from enucleation studies, as well as to gaps in the current understanding of this process., Results: Retrolaminar migration of silicone oil may be more common than previously thought, especially in at-risk patient groups, and may be associated with visual and neurologic symptoms. Some impressions regarding the cause and significance of this syndrome seem incorrect. Although this process is likely linked to postoperative elevations of intraocular pressure, the exact mechanisms of silicone entry into the subarachnoid space remain undefined. A number of anatomic factors may influence the movement of silicone from the orbit and in the various compartments of the subarachnoid space and ventricular system, resulting in variability of clinical presentations and radiologic findings. Implications for clinical decision making and directions for further research are discussed., Conclusion: Greater awareness on the part of treating physicians, systematic study of at-risk populations, and advances in imaging technology will allow further insight into this phenomenon.

Purpose: Müller's muscle conjunctiva resection is a well-established means of correcting blepharoptosis. The primary objective of this prospective study was to determine if modifying Müller's muscle conjunctiva resection by sparing the conjunctiva would accomplish successful repair while allowing patients to retain their conjunctiva. The potential advantages of preserving conjunctiva are significant and include: conservation of an anatomically normal tissue, retention of goblet cells, reduction of suture-related complications such as corneal irritation or abrasion as the conjunctiva covers the suture during postoperative healing, and preservation of conjunctiva for potential future surgical procedures critical to ocular health., Methods: This is a prospective study enrolling patients with mild to moderate ptosis., Results: The procedure has been performed in 18 patients and 30 eyelids. Follow up at 1 week revealed normal healing with expected postoperative edema and ecchymosis. Notably, all patients were free of any corneal abrasion or irritation. Follow up at 1 month and a minimum of 3 months (average 5.7 months) revealed that all patients had satisfactory correction of their blepharoptosis with Margin Reflex Distance 1 (MRD1) improvement to within 1 mm of the anticipated goal, preserved eyelid margin contour, and good symmetry (average 0.26 mm difference in MRD1 between the sides)., Conclusion: These results show an effective correction of blepharoptosis with a favorable cosmetic outcome and low postoperative complication rate; all while preserving the conjunctiva.

Purpose: To describe 2 cases of congenital corneal endothelial edema resulting from novel de novo mutations., Methods: Case A patient was a 15-month-old white child and case B patient was a 3-year-old Hispanic child presenting with bilateral cloudy corneas since birth. Clinicopathologic findings are presented. DNA samples were screened for mutations in candidate genes by Sanger sequencing., Results: Slit-lamp examination of case A patient revealed stromal edema and haze. Histology of the keratoplasty button showed stromal thickening with loss of endothelium and thin Descemet membrane. Sanger sequencing established the diagnosis of congenital hereditary endothelial dystrophy by detection of a compound heterozygous mutation in SLC4A11. The proband displayed a novel de novo frameshift mutation in one SLC4A11 allele, p.(Pro817Argfs*32), in conjunction with a maternally inherited missense mutation in SLC4A11, p.(Arg869His). Case B patient similarly presented with stromal edema and stromal haze. Histopathologic analysis revealed a spongy epithelium, focal discontinuities in Bowman layer, stromal thickening with areas of compacted posterior stroma, variable thickness of Descemet membrane, and regional multilayered endothelium. Sanger sequencing found a novel de novo nonsense mutation in the first exon of ZEB1, p.(Cys7*)., Conclusions: To the authors' knowledge, we report the earliest clinical presentation of posterior polymorphous corneal dystrophy resulting from a de novo mutation in ZEB1. Additionally, we present a congenital hereditary endothelial dystrophy case with a thin Descemet membrane with a novel compound heterozygous SLC4A11 mutation. In the absence of a family history or consanguinity, de novo mutations may result in congenital corneal endothelial dystrophies.

This case report describes a patient with known acute lymphoblastic leukemia (ALL) presenting with a rapidly enlarging and vision-threatening orbital mass. Orbital disease is rare in patients with ALL, and to our knowledge only six cases have been previously described, five of which are in children. We describe a 36-year-old Caucasian female with known acute lymphoblastic leukemia who developed markedly decreased visual acuity, proptosis, and elevated intraocular pressure over the course of 12 h. She was treated with emergent surgical intervention followed by intrathecal chemotherapy and intravenous steroids. Following medical and surgical intervention, the patient demonstrated rapid resolution of symptoms and a return to baseline visual acuity. The initial presentation of acute onset proptosis with optic nerve compromise can be suggestive of infectious etiologies, however, this case suggests caution in evaluation of patients with known systemic malignancy, particularly ALL, as early intervention with systemic steroids and surgery may result in return of visual function.

Chalazia are among the most common eyelid lesions presenting to eye care providers. Often successfully managed conservatively, some require more invasive intervention such as incision and drainage or steroid injection. Lesions that recur, do not respond to treatment, or are atypical in appearance or natural history should prompt more thorough analysis, often with biopsy and subsequent microscopic analysis. Not uncommonly, such atypical chalazia may be masking a more serious diagnosis. Eyelid cutaneous squamous cell carcinoma masquerading as a chalazion is exceedingly rare. We present a case report of an atypical chalazion that was refractory to incision and drainage as well as intralesional steroid injection. Incisional biopsy revealed the lesion to be a cutaneous squamous cell carcinoma requiring full-thickness excision and subsequent reconstruction. The patient provided written informed consent, and the contents herein are acceptable under the provisions of the institutional review board. Following Mohs excision and oculoplastic reconstruction with a Hughes flap, the patient has had a good outcome and is currently free of recurrence. Recurrent chalazia that are defiant to surgical and medical interventions should prompt biopsy and evaluation by pathology. Cutaneous squamous cell carcinoma should be considered in the differential diagnosis as early intervention can save a patient's eye and, not infrequently, their life.

We report a case of intracranial hypertension in a 13-year-old boy on levothyroxine therapy for hypothyroidism and review the literature describing this rare association. He presented with severe headaches and was found to have bilateral optic disk edema and elevated intracranial pressure shortly after an increase in his dosage of levothyroxine. The optic disk edema and headaches resolved with decreasing the levothyroxine and initiating acetazolamide., (Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

The aim of this prospective study was to conduct histopathologic and lipidomic analyses of chalazia, in order to evaluate time-dependent changes in the lesion. Samples of surgically excised chalazia were collected over a period of 12 months from 10 patients (mean age 41 years; range, 23-58) with clinically diagnosed chalazia, who underwent scheduled surgery. The ages of chalazia varied from 2 to 28 weeks. To confirm the clinical diagnoses, the morphology of collected tissue samples was evaluated histologically after hematoxylin and eosin staining. The lipids from individual chalazia were analyzed by high-performance liquid chromatography-mass spectrometry and compared with authentic lipid standards and with the lipids of meibum collected from normal controls. We observed gradual, lesion age-dependent transformation of the lipidome of chalazia from an almost normal meibum-like composition to a very different kind of lipidome. A rapid initial increase in the free cholesterol content was followed by a gradual replacement of extremely long chain meibomian-type lipids with a mixture of shorter-chain cholesteryl esters of the C14-C18 family, triacylglycerols, ceramides, phospholipids and sphingomyelins. In addition, a rapid disappearance of wax esters and cholesteryl esters of (1-O)-acyl-omega-hydroxy fatty acids from the lipidome of aging chalazia was observed. Our results are indicative of dramatic, time-dependent changes in the lesion that may involve cholesterol as a trigger and/or a marker of subsequent degeneration of the meibomian lipidome. We hypothesize that early inhibition of these transformations may be useful in reversing the course of the disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To describe a patient with Exophiala jeanselmei keratitis and to review the prior cases reported in the literature., Methods: We report one patient with keratitis after remote injury and chronic steroid use and review the six prior reported cases., Results: Culture plates from corneal scraping revealed growth of the dematiaceous fungi, E. jeanselmei, a rare causative organism of ocular infection. The patient underwent therapy with topical and intracameral antifungals and subsequently required a corneal transplant. Biopsy of the donor graft confirmed the diagnosis of E. jeanselmei. This is the first reported case to use intracameral antifungal agents and the first biopsy proven case. Half of reported cases experienced associated trauma, and severity was generally related to delay in diagnosis., Conclusions: Trauma and chronic topical steroid use contributed to the development of severe keratitis in this patient. Patients on chronic steroids should be monitored closely. Topical, subconjunctival, and intracameral antifungals have all been effective in treating this pathogen. If diagnosed and treated early, E. jeanselmei keratitis can have a good visual outcome.

Purpose: The purpose of this study was to describe a new modification for big-bubble deep anterior lamellar keratoplasty (DALK) using pneumatic pressure to detach Descemet membrane (DM) via air injection followed by ophthalmic viscoelastic device (OVD) injection., Methods: After failure of big-bubble formation after air injection, OVD was injected from a different site other than the previous air injection using a 27-gauge cannula to detach DM, called air-visco bubble (AVB) DALK technique. The technique was used in 7 human corneoscleral rims that were investigated with anterior segment optical coherence tomography and histopathology and in 69 eyes that underwent DALK surgeries., Results: Big-bubble formation was noted in 4 of 7 of the donor corneoscleral rims. The anterior segment optical coherence tomography showed big-bubble formations together with intrastromal OVD accumulation. The histology of the donor corneas showed microdetachments at the DM in the periphery, deep intrastromal separation, and big-bubble formation filled with OVD. One hundred forty-one of 210 eyes (67%) underwent successful DALK with only air injection, and 69 of 210 eyes (33%) underwent AVB technique when a big bubble was not achieved with only air injection. All the corneas showed a clear interface with good wound healing when DM was bared with the AVB DALK technique., Conclusions: Additional OVD injection to detach DM may be useful in cases where air injection fails. Also, creating small DM detachments with air injection may facilitate the formation of a big bubble with further OVD injection.

A 47-year-old healthy man presented with symptoms of double vision and drooping of the right upper eyelid. Examination disclosed signs of vertical diplopia and right upper-eyelid ptosis. An MRI delineated a well circumscribed, ring enhancing mass within the right orbit. The mass with peripheral enhancement located within the orbit, generated a broad differential diagnosis. After an excisional biopsy was performed, the mass was revealed to be fibrosis with extramedullary hematopoiesis. Current differential diagnoses of ring enhancing orbital lesions do not include extramedullary hematopoiesis, but we present a unique presentation of extramedullary hematopoiesis presenting as a ring enhancing orbital mass.

Purpose: To correlate big-bubble deep anterior lamellar keratoplasty findings in donor corneas with anterior segment optical coherence tomography (OCT) and histology., Methods: This research was conducted entirely at the University of Texas Southwestern Medical Center in Dallas, Texas. We performed deep intrastromal air injections in donor corneas on artificial chambers. Surgical patterns (big bubble, intrastromal emphysema, and perforation) were assessed by spectral domain OCT with a handheld probe and histology., Results: Surgical patterns were evaluated by histology using a novel embedding technique. A classic big bubble may be a Descemet membrane (DM) detachment with a few attached stromal fibrils. There were no large intra-DM separations as previously reported. The emphysematous surgical patterns result from intrastromal emphysema, which can be accompanied by microdetachments of DM. We saw indirect OCT signs of big bubble, but scatter from intrastromal emphysema limits deeper imaging., Conclusions: Surgical patterns of big bubble and intrastromal emphysema correlate with characteristic histology findings. Marked scatter on OCT by intrastromal emphysema limits visualization of deeper corneal structures, but the presence of a big bubble may be inferred.

Purpose: The purpose of this study was to report a case of amelanotic choroidal melanoma, previously treated with brachytherapy, subsequently exhibiting local extension through pars plana vitrectomy sites., Method: The authors present a retrospective interventional case report from a clinical practice., Results: An amelanotic choroidal melanoma, previously responsive to brachytherapy, underwent two pars plana vitrectomies for nonclearing vitreous hemorrhage with double-freeze cryotherapy to sclerotomy sites. Recurrent melanoma extended through the sclerotomies presenting as subconjunctival nodules requiring exenteration., Conclusion: Vitrectomy sclerotomy sites may serve as a route of extrascleral extension in previous brachytherapy treatment-responsive choroidal melanomas. Caution should be exercised in performing vitrectomy for choroidal melanomas with subsequent vitreous hemorrhage.

We present autopsy findings of a stillborn female infant at 20 to 21 weeks' gestation with neuroaxonal dystrophy. External examination showed features of fetal akinesia deformation sequence. Internal examination showed hypoplasia of the cerebellum, corpus callosum, and optic nerves, as well as nuclear cataracts. Light and electron microscopic examinations showed widespread axonal spheroids in the central and peripheral nervous systems. Gene sequencing failed to reveal PLA2G6 mutations, indicating that fetal neuroaxonal dystrophy presenting as fetal akinesia deformation sequence is genetically distinct from infantile neuroaxonal dystrophy and related disorders. In addition, placental examination showed α-fetoprotein-positive, eosinophilic, globular inclusions in the cytoplasm of a few villous macrophages. The significance of this novel histologic finding is unclear.

We describe a case of a 75-year-old man with diabetes type II and end-stage renal disease, presenting with a one-month history of blurring of vision in the left eye. Fundus exam showed pale and swollen optic nerve in the left eye, and temporal artery biopsy showed diffuse and extensive calcification at the internal elastic lamina and media. Biopsy of dusky erythematous lesions over the calves revealed the diagnosis of calciphylaxis. The temporal artery calcific lesions should hence be differentiated from the less extensive atherosclerotic changes, which mainly affect the media of the artery, as it is crucial to suspect this life-threatening diagnosis in patients at risk.

Purpose: To report the clinical and histopathologic findings of 2 patients who developed epithelial downgrowth after Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: A 64-year-old woman (case 1) underwent DSAEK for corneal edema secondary to Fuchs endothelial dystrophy in left eye. However, the graft failed to attach, and a repeat DSAEK was performed 3 weeks later. After 4 months, the patient developed herpes simplex virus keratitis that resulted in anterior stromal scarring. A penetrating keratoplasty was performed 15 months after the initial DSAEK. Our second patient (case 2) was an 87-year-old female who underwent DSAEK for corneal edema secondary to Fuchs endothelial dystrophy in left eye. Six months later, she had an episode of graft rejection and developed secondary glaucoma. At 14 months postoperatively, a retrocorneal membrane was seen involving the temporal half of the endothelial surface of the graft. The retrocorneal membrane extended from the inferior thickened edge of the endothelial keratoplasty graft to the iris stromal surface. An Ahmed shunt implantation followed by repeat DSAEK were then performed. The excised corneal buttons were examined., Results: Histopathologic evaluation showed multilayered epithelium on the interface and attenuated endothelium in the endothelial graft in case 1. The host cornea showed diffuse stromal scarring. Case 2 showed multilayered epithelium with early cyst formation at the edge of the graft. The epithelium extended to involve the endothelial surface without involvement of interface surface. Significant scar formation was observed between the edge of the endothelial keratoplasty graft and thickened host Descemet membrane. Some pigmented cells were present within the epithelial downgrowth. The epithelium stained positively with cytokeratin A1/A3 in both cases., Conclusions: Although rare, epithelial downgrowth can occur after DSAEK and can be associated with graft failure. Early recognition and surgical treatment of epithelial downgrowth is crucial in treating the complications of corneal decompensation and glaucoma.

Objectives: To report an important complication of ocular evisceration therapy for blind, painful eyes that has been unreported in the literature, and to stress the need for careful preoperative evaluation to exclude occult neoplasms prior to therapy., Design: Multicenter, retrospective, nonrandomized clinicopathological case series of patients found to have previously unsuspected uveal malignant melanoma during histopathological examination of blind, painful eyes treated by evisceration., Results: Histopathological examination of evisceration specimens disclosed previously unsuspected uveal melanoma in 7 patients who were treated for blind, painful eyes. Inflammation caused by necrosis of the tumor and other ocular tissues led to misdiagnosis as endophthalmitis, orbital cellulitis, or idiopathic orbital inflammation in several cases. Preoperative imaging was not performed in 3 cases and failed to detect tumors in the remaining 4 cases. Failure of necrotic tumors to enhance contributed to misdiagnosis., Conclusions: The presence of a malignant intraocular neoplasm should be excluded prior to evisceration of any blind eye or blind, painful eye, particularly with opaque media. Necrosis-related inflammation can confound the clinical diagnosis of occult lesions, as can failure of necrotic tumors to enhance on imaging studies.

Purpose: To assess the expression of PD-L1 and PD-L2 on human ocular cells and their potential to regulate ocular inflammation., Methods: Five categories of human ocular cells were evaluated for PD-L1 and PD-L2 expression by RT-PCR and flow cytometry. Three normal eyes and an inflamed eye from a patient with sympathetic ophthalmia were examined by immunohistochemistry for in situ PD-L1 expression. The immunomodulatory functions of PD-L1 and PD-L2 were tested by coculturing untreated or IFN-gamma-pretreated ocular cells with activated human peripheral blood T cells for 48 hours and assessing T-cell production of IFN-gamma, TNF-alpha, IL-4, and IL-5 by ELISA and T-cell apoptosis by flow cytometry., Results: PD-L1 protein was expressed constitutively in 4 of 5 human ocular cell lines, and its expression was significantly upregulated after stimulation by IFN-gamma. Moreover, in situ expression of PD-L1 in inflamed ocular tissues was remarkably upregulated compared with normal eyes. Although PD-L2 expression was detectable by flow cytometry on 3 of 5 ocular cell lines, immunohistochemical staining did not show expression of PD-L2 on either normal or inflamed ocular tissues. IFN-gamma, TNF-alpha, and IL-5 production by activated T cells cocultured with ocular cells was significantly enhanced in the presence of anti-PD-L1 blocking antibody. However, ocular cell-expressed PD-L1 and PD-L2 did not induce T-cell apoptosis., Conclusions: PD-L1 expressed on human ocular cells has a presumptive role in controlling ocular inflammation by inhibiting the production of proinflammatory cytokines and a Th2 cytokine by activated T cells. This may represent an important mechanism for maintaining immune privilege in the eye.

Purpose: To study the nature of the deposits in Avellino corneal dystrophy (ACD) worsening after laser in situ keratomileusis (LASIK), and suggest a mechanism for histopathogenesis., Design: Interventional case report., Methods: A 28-year-old woman previously diagnosed with bilateral ACD underwent bilateral LASIK. The corneal dystrophy progressively worsened bilaterally, one year later. A penetrating keratoplasty was subsequently performed on the right eye at 31 years of age, and in the left eye a year later. The clinical and histopathologic findings of the corneal graft of the right eye were reported in the literature, with positivity to the Masson trichrome stain, negative staining with Congo red, and heterozygosity for the Arg124His mutation by serum DNA studies. Histopathologic studies of the corneal graft of the left eye were conducted at the University of Texas Southwestern Medical Center., Results: Histopathologic examination of the excised cornea showed the Masson trichrome positive deposits present from underneath the Bowman layer to the LASIK interface, with absence of deposits posterior to the latter. In contrast to the prior report describing findings in the corneal graft of the left eye, the deposits stained lightly with Congo red, but failed to show birefringence under polarized light, or fluorescence with thioflavin T., Conclusion: Accelerated deposits developing after LASIK in ACD eyes seem to harbor pre-amyloid features. The epithelium is likely to be the culprit, in a pathway independent of with human transforming growth hormone beta (TGF-beta), with deposits developing in the anterior stroma and the stromal interface.

Purpose: To report the clinical, histopathologic, and confocal findings of corneal siderosis., Methods: A 35-year-old man presented after a car battery explosion with diffuse left corneal anterior stromal pigment deposition and an intraocular metallic foreign body of the left iris. The corneal pigment was analyzed by confocal microscopy and a lamellar corneal biopsy., Results: Confocal microscopy showed the pigment to be highly reflective material in the corneal stroma with greatest density anteriorly. Histologic examination revealed the pigment to be iron with a diagnosis consistent with corneal siderosis., Conclusions: Corneal biopsy with Prussian blue established siderosis as the etiology of corneal pigmentation. A short delay in the removal of the foreign body contributed to the development of siderosis. The location of the foreign body on the iris may account for the predominant corneal involvement and relative sparing of the retina. Confocal microscopy may be useful in the evaluation of corneal siderosis.

Objective: To examine the lowland gorilla (Gorilla gorilla gorilla) eye and determine similarities to and differences between the mountain gorilla (Gorilla gorilla beringei) and the human eye. In addition, we compare our findings of G. g. gorilla to previous reports on the eye of this subspecies., Procedures: A 13-year-old deceased male lowland gorilla and a 34-year-old deceased female lowland gorilla were included in the study. Gross and microscopic examinations of the formalin-fixed right eyeball of each gorilla were carried out., Results: Globe dimensions of G. g. gorilla were similar to G. g. beringei and to humans. The limbal conjunctival epithelium and the choroid were densely pigmented. However, the distribution of the conjunctival pigment ring was different to that of G. g. beringei and the melanocytes of the choroid were unusually round. There were deep crypts in the anterior border layer of the iris, and the epithelium of the pars plana was uniquely irregular. Vertical corneal diameter was observed to be equal or greater than horizontal diameter in G. g. gorilla, which is in contrast to humans and to previous findings for G. g. beringei. Corneal thickness was closer to that of humans than to G. g. beringei. Posterior lens capsule thickness was noticeably greater than that of humans., Conclusions: Although some variation between the ocular anatomy of G. g. gorilla and G. g. beringei does exist, the gross and microscopic findings closely resemble each other in these two subspecies. In addition, the eye of Gorilla appears remarkably similar to the human eye. However, comparison of measurements with those in humans is somewhat limited because formalin-fixation can introduce tissue shrinkage and artifact.

Autophagy is commonly observed in metazoan organisms during programmed cell death (PCD), but its function in dying cells has been unclear. We studied the role of autophagy in embryonic cavitation, the earliest PCD process in mammalian development. Embryoid bodies (EBs) derived from cells lacking the autophagy genes, atg5 or beclin 1, fail to cavitate. This defect is due to persistence of cell corpses, rather than impairment of PCD. Dying cells in autophagy gene null EBs fail to express the "eat-me" signal, phosphatidylserine exposure, and secrete lower levels of the "come-get-me" signal, lysophosphatidylcholine. These defects are associated with low levels of cellular ATP and are reversed by treatment with the metabolic substrate, methylpyruvate. Moreover, mice lacking atg5 display a defect in apoptotic corpse engulfment during embryonic development. We conclude that autophagy contributes to dead-cell clearance during PCD by a mechanism that likely involves the generation of energy-dependent engulfment signals.

Objective: To describe a newly recognized clinical syndrome in Acanthamoeba keratitis consisting of severe reactive ischemic posterior segment vascular inflammation., Design: Noncomparative, retrospective, single-institution observational case series., Participants: Five eyes of 5 patients with Acanthamoeba keratitis., Methods: A retrospective review of the records of patients diagnosed with Acanthamoeba keratitis between January 1, 1995, and December 1, 2005, was conducted to identify those who underwent eventual enucleation. Five enucleated eyes of 118 eyes with Acanthamoeba keratitis were identified., Main Outcome Measures: History, clinical examination results, available laboratory study results, and histopathologic examination results., Results: Histopathologic examination showed Acanthamoeba cysts in the cornea in 4 eyes, whereas it failed to demonstrate amebic cysts or trophozoites in the posterior segment of all eyes studied and unexpectedly revealed chronic chorioretinal inflammation with perivascular lymphocytic infiltration and diffuse neuroretinal ischemia in 4 of 5 eyes. Retinal artery thrombosis was present in 3 of the 4 involved eyes, and central retinal artery and vein thrombosis was found in 1 eye. Hematologic studies in 3 patients showed abnormal anticardiolipin antibody levels in 1 patient and factor V Leiden deficiency in another., Conclusions: Prolonged Acanthamoeba keratitis can result in a severe sterile ischemic posterior segment inflammation that is potentially blinding, especially in patients with underlying hypercoagulation disorders.

Purpose: To describe the association of acanthamoeba keratitis and glaucoma, to establish an incidence of glaucoma in patients with acanthamoeba keratitis, to discuss treatment options and outcomes in these patients, and to describe the histopathologic findings and pathogenesis of glaucoma secondary to acanthamoeba keratitis., Methods: After Institutional Review Board approval, the charts of all patients suspected of having acanthamoeba keratitis at Aston Ambulatory Center at The University of Texas Southwestern Medical Center were reviewed. Inclusion criteria were as follows: diagnosis of acanthamoeba keratitis by positive confocal microscopy or culture, diagnosis of glaucoma or ocular hypertension secondary to acanthamoeba keratitis, and at least 6 months of follow-up. Exclusion criteria included a previous diagnosis of glaucoma or ocular hypertension and any history of intraocular surgery before the development of glaucoma. The date of keratitis development, pneumotonometry on initial and follow-up examinations, glaucoma medications used, and surgical procedures performed were tabulated., Results: Twenty patients (20 eyes) were included. Six (30%) eyes developed secondary glaucoma during the review period. Of the patients treated for glaucoma with medication alone, the visual acuity of three (75%) of four became light perception or no light perception. Three of six patients required glaucoma drainage device implantation for intraocular pressure control. Of these, the vision of one eye became no light perception, and the other two eyes maintained better than 20/100 vision. Histopathologic examination showed chronic inflammation of the trabecular meshwork and angle closure. No acanthamoeba organisms were found in the angle structures., Conclusions: The development of secondary glaucoma is not uncommon in acanthamoeba keratitis and is a poor prognostic sign in patients with acanthamoeba keratitis, because most progress to light perception or no light perception vision. Histopathologic findings suggest an inflammatory angle-closure mechanism, apparently without direct infiltration of the organism. The glaucoma associated with acanthamoeba keratitis is often severe and frequently requires surgical intervention for intraocular pressure control and vision preservation.

Objective: The pathologic markers of nonaccidental injury (NAI) of the central nervous system (CNS) of infants and young children include subdural, subarachnoid, and retinal hemorrhages. Immunohistochemical staining for beta-amyloid precursor protein (betaAPP) has been used to investigate traumatic axonal injury of the brain, brain stem, and spinal cord injuries, and has potential as an additional indicator of traumatic head injury. A single study has reported that betaAPP immunostaining of the optic nerve in CNS NAI reveals axonal damage. The purpose of our study was to explore further the utility of betaAPP immunostaining of optic nerves for the detection of traumatic axonal injury., Methods: We used hematoxylin-eosin and betaAPP immunostaining to evaluate the eyes and optic nerves in 18 cases of CNS nonaccidental blunt force head injury, 4 cases of homicidal blunt force abdominal injury (BFAI), 1 homicidal suffocation, 1 case of sudden infant death syndrome, 1 near-drowning, 1 overlay (clinical history: "found under sleeping mother in bed"), 1 motor vehicle accident, and 6 natural deaths in children < or =5 years of age., Results: Evaluation of the cases of CNS NAI revealed 17 of 18 (94%) with subdural hemorrhage; 15 of 18 (83%), subarachnoid hemorrhage; 17 of 18 (94%), retinal hemorrhage; 16 of 18 (88%), perioptic nerve hemorrhage; and 6 of 18 (33%), optic nerve betaAPP immunoreactive axonal swellings. The only nontraumatic case that demonstrated betaAPP immunoreactive axonal swellings was the near-drowning. No cases of BFAI, suffocation, overlay, or natural deaths revealed any retinal or perioptic nerve hemorrhage or significant optic nerve betaAPP immunoreactivity. Global hypoxic-ischemic injury was present in 21 cases, of which 19 had evidence of brain swelling, and 7 demonstrated betaAPP immunoreactive axonal swellings., Conclusions: These findings confirm the presence of optic nerve axonal injury in some cases of fatal pediatric CNS NAI.

Prions are small proteinaceous infectious agents known to cause central nervous system infections in both animals and humans. Interest in the pathogenesis of these diseases has grown since the emergence of bovine spongiform encephalopathy (BSE or "mad cow disease") in the United Kingdom and several other countries in Europe. Ingestion of meat products from animals infected with BSE has resulted in transmission of the disease to humans as a variant form of Creutzfeldt-Jakob Disease (vCJD). CJD has a long asymptomatic incubation period, is untreatable, and universally fatal. Hence concern has arisen over other possible routes of disease transmission. Because it is known that prions are found in low levels in the corneas of animals with experimentally induced prion disease, and that a case of human CJD transmission by corneal transplantation has occurred, the question of possible prion transmission through the reuse of diagnostic fitting of contact lenses has surfaced. This article reviews prion diseases of animals and humans, and the data regarding the presence and location of prions in the eye. Issues inherent in the question of corneal and contact lens transmission are discussed. Although some key information has yet to be derived, it appears that the chance of obtaining prion disease through contact lens use is negligible.

Purpose: Removing central corneal pathology often leads to a hyperopic shift secondary to corneal flattening. A myopic shift, or reduction in hyperopia, would be expected after removal of peripheral corneal pathology with central corneal steepening. This case illustrates the refractive changes induced by Salzmann's nodular degeneration and the myopic shift associated with their excision., Methods: A 53-year-old female presented with a slowly progressive increase in hyperopia. Vision in the right eye was 20/40 with a refraction of +10.00 -4.00 x 90 degrees. Vision in the left eye was 20/30 with a refraction of +5.75 -2.00 x 105 degrees. Both corneas exhibited nodular subepithelial opacities in the mid-periphery. A superficial keratectomy was performed on each eye, 1 year apart., Results: Twelve days postoperatively, uncorrected visual acuity in the right eye was 20/25, and 20/20 with a refraction of -0.75 -0.50 x 31 degrees, 6 months later. Six days postoperatively, uncorrected visual acuity in the left eye was 20/40, and 20/30 with a refraction of -1.25 D, 1 month later., Conclusion: Superficial keratectomy provides a means of restoring the original corneal contour, especially when the pathology is easily dissected from Bowman's layer. The surgeon should investigate the refractive status prior to the development of the nodules and be aware of the possible refractive change upon removal of the pathology.

Objectives: To quantify the risk of Creutzfeldt-Jakob disease (CJD) among cornea donors, evaluate supplemental screening strategies, and address concerns about the adequacy of current methods of screening tissue donors in the United States., Methods: Reported data on deaths due to CJD and from all causes were used to estimate the rate of CJD among cornea donors. The impact of increased screening on risk of CJD and donor supply was evaluated., Results: Only 1.3 of the approximately 45 000 cornea donors in the United States each year might be expected to have CJD. Most of the estimated risk (91%) is due to preclinical (asymptomatic) disease and therefore could not be eliminated by screening for signs or symptoms. If only the highest-risk age group (60 to 69 years) were screened and specificity were 90%, more than 21 000 otherwise acceptable donors would incorrectly be excluded over a period of 17.5 years to correctly exclude a single donor with symptomatic CJD., Conclusions: Currently, the risk of CJD transmission following cornea transplantation is remarkably low. Screening for symptoms of CJD would have minimal impact on safety, but would reduce donor supply and likely result in many patients not receiving needed treatment.