Sudden Death in a Child With Ocular Lesions.

This case report describes a patient treated for ocular lesions who died suddenly at age 8 years and was diagnosed postmortem with Carney complex.

A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance.

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology centers. Adequate conjunctival biopsies were stained with hematoxylin and eosin, Melan-A, SOX10, and PReferentially expressed Antigen in Melanoma. Digitized slides were uploaded on the SmartZoom platform and independently scored by 4 ocular pathologists to obtain a consensus score, before circulating to 14 expert eye pathologists for independent scoring. In total, 105 cases from 97 patients were evaluated. The initial consensus diagnoses using the WHO-EYE04 C-MIL system were as follows: 28 benign conjunctival melanoses, 13 low-grade C-MIL, 37 high-grade C-MIL, and 27 conjunctival MIS. Using this system resulted in 93% of the pathologists showing only fair-to-moderate agreement (kappa statistic) with the consensus score. The WHO-EYE05 C-MIL system (with high-grade C-MIL and MIS combined) improved consistency between pathologists, with the greatest level of agreement being seen with benign melanosis (74.5%) and high-grade C-MIL (85.4%). Lowest agreements remained between pathologists for low-grade C-MIL (38.7%). Regarding WHO-EYE05 C-MIL scoring and clinical outcomes, local recurrences of noninvasive lesions developed in 8% and 34% of the low- and high-grade cases. Invasive melanoma only occurred in 47% of the cases that were assessed as high-grade C-MIL. This extensive international collaborative study is the first to undertake a comprehensive review of the WHO-EYE05 C-MIL scoring system, which showed good interobserver agreement and reproducibility.

Microbial profile of lacrimal system Dacryoliths in American Midwest patient population.

PURPOSE: Dacryoliths of the canalicular pathway are classically attributed to Actinomyces species as the most common organism. However, global shifts toward Streptococcus and Staphylococcus species have been reported. The objective of this article is to update the American Midwest epidemiology of lacrimal system dacryoliths for targeted clinical treatment. MATERIALS AND METHODS: A retrospective chart review from January 2015 to 2021 of patients with a history of surgical procedure for lacrimal removal of dacryolith for canaliculitis, canalicular obstruction, dacryocystitis, and nasolacrimal duct obstruction was included. Specimens were sent for histopathological evaluation and microbial culture. RESULTS: A total of 48 specimens were included. The most common organism isolated for canalicular pathology was Actinomyces spp (23%), followed by Staphylococcus spp (21%) and Streptococcus spp (19%). Histopathological staining accounted for 45% of Actinomyces isolation when culture data inconclusive. In a subgroup analysis of lacrimal sac dacryoliths, the most common organism was Staphylococcus spp (29%). Actinomyces species were not isolated from the lacrimal sac or nasolacrimal duct. CONCLUSION: Actinomyces maintains a microbial predominance in canalicular dacryoliths and requires careful culture and histopathological analysis for its fastidious nature. Lacrimal sac and nasolacrimal duct dacryolith found no isolates of Actinomyces, and the most common organism was Staphylococcus.

Globe dislocation and optic nerve avulsion following all-terrain vehicle accidents.

Purpose: Open-air motor vehicles present unique trauma risks to the eyes and face. We describe two patients who suffered a crash while riding an all-terrain vehicle (ATV), leading to globe dislocation with optic nerve avulsion in order to raise awareness about the risks associated with ATV accidents. Observations: In both cases, the injury was caused by high-speed trauma to the orbit involving a tree branch. One patient sustained a life threatening arrythmia requiring a short stay in the intensive care unit, and both patients required emergent surgical management and eventual socket reconstruction. Conclusions and Importance: These cases highlight the need for greater advocacy on behalf of rider safety. The authors encourage ophthalmologists to counsel patients who use ATVs to wear helmets, seatbelts, and protective eyewear to prevent these types of injuries in the future.

Validation of the Newly Proposed World Health Organization Classification System for Conjunctival Melanocytic Intraepithelial Lesions: A Comparison with the C-MIN and PAM Classification Schemes.

PURPOSE: We sought to compare the sensitivity, specificity, accuracy, and interobserver agreement of the two most commonly used classification systems for conjunctival melanocytic intraepithelial lesions with the new World Health Organization (WHO) classification. DESIGN: Retrospective case series and evaluation of classification systems. METHODS: We reviewed the pathology and medical records of all patients who underwent a primary biopsy procedure for conjunctival primary acquired melanosis (PAM) at Wills Eye Hospital between 1974 and 2002 who had ≥36 months of follow-up. Data collected included age, sex, clinical findings, recurrence, and progression to melanoma. Twelve ophthalmic pathologists analyzed scanned hematoxylin and eosin-stained virtual microscopic slides using 3 classification systems: PAM, conjunctival melanocytic intraepithelial neoplasia, and the WHO 4th edition classification of conjunctival melanocytic intraepithelial lesions. Observer agreement, sensitivity, specificity, and diagnostic accuracy of each classification system were assessed. RESULTS: There were 64 patients who underwent 83 primary excisions with cryotherapy for conjunctival PAM who had adequate tissue for histopathologic evaluation. The interobserver agreement in distinction between the low- and high-grade lesions was 76% for PAM, 67% for conjunctival melanocytic intraepithelial neoplasia, and 81% for WHO classification system. Low-grade lesions provided the greatest interpretative challenge with all 3 classification systems. The 3 classification systems had comparable accuracy of 81%-83% in their ability to identify lesions with potential for recurrence. CONCLUSIONS: This study highlights the comparable strengths and limitations of the 3 classification systems for conjunctival melanocytic intraepithelial lesions and suggests that the simplified WHO classification scheme is appropriate for evaluation of these lesions.

Optical Coherence Tomography Characteristics of the Choroid Underlying Congenital Hypertrophy of the Retinal Pigment Epithelium.

PURPOSE: This study evaluates and characterizes the choroid underlying congenital hypertrophy of the retinal pigment epithelium (CHRPE). METHODS: Retrospective observational study of CHRPE at least 2 mm in diameter. Choroidal vascular architecture was qualitatively examined. Choroidal thickness was measured by 2 independent observers using enhanced depth imaging spectral domain optical coherence tomography. RESULTS: Forty-six eyes of 46 patients with CHRPE were included. Thirty-two lesions had imaging sufficient for analysis. Haller's layer was healthy in 18 (56%), thin in 13 (41%), and absent in 1 (2%). Sattler's layer was atrophic in 30 (94%), and choriocapillaris was atrophic in 31 (97%). CHRPE with thinned Haller's layer had significantly larger diameter. The mean sub-CHRPE choroidal thickness was 82.4 ± 7.9 µm, compared to a thickness of 148.4 ± 9.6 µm in the normal adjacent choroid (p < 0.0001). Mean retinal thickness overlying the CHRPE was 77.3 ± 4.3 µm, compared to a retinal thickness of 137.8 ± 2.9 µm overlying the normal adjacent choroid (p < 0.0001). Sub-CHRPE choroidal thickness was a mean of 56.2 ± 3.1% of the adjacent normal choroidal thickness. CONCLUSION: The underlying choroid CHRPE is thinner than the adjacent normal choroid. All layers of the choroid can be thin with a preference of the inner Sattler's and choriocapillaris layers.

GNAQ Mutations in Diffuse and Solitary Choroidal Hemangiomas.

PURPOSE: GNAQ mutations have been identified in port wine stains (both syndromic and nonsyndromic) and melanocytic ocular neoplasms. This study investigates the presence of GNAQ mutations in diffuse (those associated with Sturge-Weber syndrome [SWS]) and solitary choroidal hemangiomas. PARTICIPANTS: Tissue from 11 patients with the following diagnoses: port wine stain (n = 3), diffuse choroidal hemangioma (n = 1), solitary choroidal hemangioma (n = 6), and choroidal nevus (n = 1). METHODS: Ten specimens were interrogated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, a hybridization capture-based next-generation sequencing assay for targeted deep sequencing of all exons and selected introns of 468 key cancer genes in formalin-fixed, paraffin-embedded tumors. Digital polymerase chain reaction was used to detect GNAQ Q209 mutation in 1 specimen. MAIN OUTCOME MEASURES: Detection of GNAQ codon-specific mutation. RESULTS: Activating somatic GNAQ mutations (c.547C > T; p.Arg183Cys) were found in 100% (3 of 3) of the port wine stain and in the diffuse choroidal hemangioma. Somatic GNAQ mutations (c.626A > T; p.Gln209Leu) were found in 100% (6 of 6) of the solitary choroidal hemangiomas and (c.626A > C; p.Gln209Pro) in the choroidal nevus. CONCLUSIONS: GNAQ mutations occur in both diffuse and solitary hemangiomas, although at distinct codons. An R183 codon is mutant in diffuse choroidal hemangiomas, consistent with other Sturge-Weber vascular malformations. By contrast, solitary choroidal hemangiomas have mutations in the Q209 codon, similar to other intraocular melanocytic neoplasms.

Embarking on a Journey of Discovery: Developing Transitional Skill Sets through a Scholarly Concentration Program.

PROBLEM: Medical student participation in research enhances appreciation of the scientific literature and the conduct of investigation, and may lead to an interest in academic medicine. Independent medical student research offers frequently overlooked opportunities to develop and assess professional practice abilities, including project design and implementation, interprofessional team communication, and time management. These skills, useful to physicians, are often challenging for medical students to master as they transition into clinical careers. To address this challenge, we designed and embedded interventional modalities into a highly mentored and longitudinal scholarly concentration component of the curriculum. INTERVENTION: The Embark scholarly concentration program incorporates traditional research training with the development of professional practice skills essential for transitioning to clinical practice. The program includes individualized and just-in-time components enabling student access to information and feedback specific to their projects and development of professional practice skills. CONTEXT: The Embark program is a required longitudinal component of the Oakland University William Beaumont School of Medicine undergraduate medical curriculum. The Embark program consists of courses that inform and facilitate a required longitudinal independent research project. OUTCOME: A retrospective evaluation of the Embark program's success with development of professional practice skills through the lens of both faculty and student perceptions included analysis of project records and course evaluation feedback. Evaluation of individual student development of transitional skill ability is possible through both quantitative and qualitative analysis of data collected from student project records. More than 80% of course evaluation commentary on strengths of the program addressed activities related to professional practice skills. To systematize the evaluation of these data sources, we have piloted a framework, iSAIL, designed to assess student development in these skills during the planning and conduct of a research project. LESSONS LEARNED: By developing professional practice skills in the context of a scholarly concentration program, medical students can build a foundation for future engagement in research while they develop skills to overcome challenges that they are likely to encounter in their clinical careers. Modalities designed to evaluate individualized student development of professional practice skills through research participation define program successes and may lead to the identification of additional resources needed by students. By offering medical students opportunities to develop professional practice skills within the protected environment of an independent research project, this scholarly concentration program provides a valuable opportunity to influence the early development of skills necessary throughout their clinical careers.

Dealing With Deans and Academic Medical Center Leadership: Advice From Leaders.

The 2017 Association of Pathology Chairs Annual Meeting included a session for department chairs and other department leaders on "how to deal with deans and academic medical center leadership." The session was focused on discussing ways to foster positive relationships with university, medical school, and health system leaders, and productively address issues and opportunities with them. Presentations and a panel discussion were provided by 4 former pathology chairs who subsequently have served as medical deans and in other leadership positions including university provost, medical center CEO, and health system board chair. There was a strong consensus among the participants on how best to deal with superiors about problems, conflicts, and requests for additional resources and authority. The importance of teamwork and accountability in developing a constructive and collaborative relationship with leaders and peers was discussed in detail. Effectiveness in communication, negotiation, and departmental advocacy were highlighted as important skills. As limited resources and increased regulations have become growing problems for universities and health systems, internal stress and competition have increased. In this rapidly changing environment, advice on how chairs can interact most productively with institutional leaders is becoming increasingly important.

Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: A Clinical-Pathophysiological Analysis.

PURPOSE: To derive novel insights into the pathophysiology of vancomycin-related hemorrhagic occlusive retinal vasculopathy (HORV) through a careful clinicopathologic correlation. METHODS: We retrospectively reviewed the clinical and pathologic course of 2 consecutive patients who developed HORV. The clinical history, multimodal imaging, ultrasound biomicroscopy (UBM), and intraoperative and histologic findings are reported. RESULTS: Both patients presented with decreased vision and eye pain within 1 week following otherwise uncomplicated cataract extraction and were diagnosed with HORV after endophthalmitis was ruled out. Both patients presented with significant ocular discomfort that progressively worsened, and both experienced a dismal visual outcome despite early aggressive medical and surgical therapy. One patient requested enucleation for a blind and painful eye. Upon histologic examination of this eye, the iris and ciliary body appeared to be infarcted with separation of the iris and ciliary epithelia from their adjacent stromal components. These findings were corroborated by UBM of the second patient. Histologic examination of the posterior segment demonstrated severe hemorrhagic necrosis of the neurosensory retina and an occlusive nonarteritic vasculopathy of the retina and choroid. The choroid was thickened by prominent nongranulomatous chronic inflammation accompanied by a glomeruloid proliferation of small vessels. The inflammatory infiltrate was almost exclusively confined to the choroid and consisted of predominantly T cells. There was conspicuous absence of inflammatory cells in the retina and no histologic evidence of leukocytoclastic vasculitis. CONCLUSIONS: HORV is a rare condition that can lead to profound vision loss. Significant ocular pain can be a presenting sign of HORV in cases with severe iris and ciliary body ischemia. Although it has been suggested that HORV is a form of leukocytoclastic retinal vasculitis, the histologic findings herein indicate that the pathophysiology is more complex. It is grounded in a necrotizing retinal vasculopathy in the absence of retinal vasculitis, chronic nongranulomatous choroiditis, and an unusual glomeruloid proliferation of endothelial cells in the choroid and elsewhere in the eye.

Growth of Uveal Melanoma following Intravitreal Bevacizumab.

PURPOSE: Typically treatment of large melanomas (by Collaborative Ocular Melanoma Study criteria) is restricted to enucleation, due to size constraints for plaque brachytherapy. Because primary and metastatic uveal melanoma cells are inhibited by bevacizumab (an anti-vascular endothelial growth factor), this prospective study evaluated the impact of intravitreal bevacizumab on large uveal melanomas that were destined for enucleation. Size reduction by bevacizumab would potentially salvage these eyes by making them eligible for treatment with plaque brachytherapy. PROCEDURES: Two patients with large uveal melanoma were each treated with one intravitreous injection of bevacizumab (1.25 mg/0.05 mL). RESULTS: Both tumors displayed paradoxical growth 1 week following the injection, with confirmed growth 1 week later (increase from baseline of 1.1 mm in one eye and 3.1 mm in the other eye). Both eyes were enucleated and monosomy 3 and vasculogenic mimicry patterns were identified in both tumors. At 9 years follow-up, both patients were alive and metastasis free. CONCLUSION: These patients demonstrate that neoadjuvant intravitreous bevacizumab does not decrease the size of large uveal melanomas and may, in fact, result in their paradoxical growth. This observation supports a cautious approach in the use of intravitreous bevacizumab for uveal melanoma, particularly in the neoadjuvant setting.

MULTIMODAL IMAGING AND HISTOLOGIC CORRELATION OF ISOLATED METASTASIS OF PROSTATE ADENOCARCINOMA TO THE CHOROID.

PURPOSE: To provide correlative clinical-multimodal imaging-histopathologic findings of isolated prostatic choroidal metastasis. METHODS: Ophthalmologic examination, fluorescein angiogram, spectral-domain optical coherence tomography, fundus autofluorescence, computerized tomography, magnetic resonance imaging, positive emission tomography, CSF analysis, serologies, tissue pathology with immunohistochemistry, and examination of relevant literature. RESULTS: A 76-year-old man with a history of prostate adenocarcinoma was referred for 2 months of unilateral blurry vision. Fundus examination revealed elevated deep orange choroidal lesions in the macula with overlying retinal pigment epithelium mottling and subretinal fluid. Fluorescein angiogram demonstrated alternating areas of hypofluorescence and hyperfluorescence (staining) without leakage. Optical coherence tomography revealed dome-shaped and lumpy choroidal lesions with surrounding undulating "lumpy bumpy" and "rippled/seasick" patterns. Workup for a primary or additional metastatic lesion including computerized tomography of head/chest/abdomen/pelvis, lumbar puncture, magnetic resonance imaging brain, and whole-body positive emission tomography scan was negative. Full-thickness excisional chorioretinal biopsy was obtained through pars plana vitrectomy with diathermy and vertical scissors. Histologic examination revealed adenocarcinoma with weak positive staining for prostate specific antigen, moderate positive staining for P501S (prostein), and strong positive staining for prostatic acid phosphatase, consistent with metastasis from a prostate primary. Treatment consisted of local radiation with regression of the metastatic tumor. The patient is also on concomitant androgen deprivation treatment because there is a very high incidence of systemic recurrence due to hematogenous involvement. The patient's vision has continued to improve 6 months past treatment. CONCLUSION: The authors present a unique case to highlight the multimodal imaging and histology of a rare presentation of biopsy-proven, isolated metastasis of prostate adenocarcinoma to the choroid. Systemic workup is required, and if unrevealing of a primary or metastatic lesion, full-thickness chorioretinal biopsy and histopathology can provide a definitive diagnosis, allowing optimal treatment. Chorioretinal biopsy is a useful technique and may allow for visual preservation while also giving superior histologic quality.