Bilateral Choroidal Detachments following Novel CAR T-Cell Immunotherapy Regimen.

PURPOSE: To describe a vision-threatening adverse event of a novel CAR T-cell immunotherapy for metastatic prostate cancer. METHODS: Observational Case Report. PATIENT: 77-year-old male with history of metastatic prostate cancer and pulmonary embolism enrolled in a clinical trial investigating the use of CAR T-cell immunotherapy for treatment of metastatic prostate cancer presented with a subjective left temporal visual disturbance. RESULTS: The patient was found to have bilateral extensive choroidal detachments on examination. OCT macula demonstrated no intraretinal fluid or supraretinal fluid in both eyes. B-scan of both eyes redemonstrated choroidal detachments in both eyes and no retinal detachment in either eye. The patient was initiated on a topical and systemic steroid regimen and experienced symptomatic and clinical improvement. CONCLUSION: We exhibit a case of bilateral choroidal detachments secondary to systemic reaction to a novel immunotherapy for metastatic cancer successfully treated with systemic and topical steroids. Close follow up may be required for patients receiving similar novel immunotherapeutic regimens.

Bilateral uveitis, retinal periphlebitis, and optic neuritis associated with non-pineal central nervous system germinoma.

PURPOSE: To report a case of bilateral uveitis, retinal periphlebitis, and optic neuritis associated with a non-pineal central nervous system (CNS) germinoma. METHODS: Case report. RESULTS: A 32-year-old male presented with episodes of acute painless visual disturbance in each eye, and was found to have decreased visual acuity, abnormal color vision, an afferent pupillary defect in the left eye, bilateral optic disc edema, perivenous sheathing, and candle-wax dripping exudates. Optical coherence tomography revealed bilateral intraretinal fluid and posterior vitreous hyperreflective opacities. Fluorescein angiography revealed bilateral optic disc leakage without active small vessel leakage. Magnetic resonance imaging of the brain and orbits revealed enhancing periventricular lesions and enhancement of the left optic nerve and bilateral perioptic nerve sheaths, posterior globes, and optic nerve heads. Brain biopsy was consistent with a CNS germinoma. His ocular signs and symptoms improved with chemotherapy for the germinoma. CONCLUSION: CNS germinomas, including those located outside the pineal region, can be associated with optic neuritis, uveitis, and periphlebitis including characteristic candle-wax dripping exudates. Ocular signs and symptoms typically improve with treatment of the underlying germinoma.

CENTRAL RETINAL ARTERY OCCLUSION AS PRESENTATION OF BARTONELLA ENDOCARDITIS.

BACKGROUND/PURPOSE: To describe a rare ocular presentation of a systemic illness and the important lifesaving diagnosis made by a complete eye examination. METHODS: The patient was evaluated with a comprehensive ophthalmic examination and followed closely in the outpatient setting with optical coherence tomography, fluorescein angiography, and color fundus photos. RESULTS: A 66-year-old man presented with acute vision loss of the left eye. A complete eye examination revealed that he had a central retinal artery occlusion. Systemic workup revealed that he had a mitral valve vegetation and blood cultures grew Bartonella henselae. His kidney biopsy showed membranoproliferative glomerulonephritis, which is often seen with septic emboli. Furthermore, the patient lacked any ocular inflammatory signs. This constellation of findings was diagnostic for a thromboembolic etiology causing his central retinal artery occlusion. At follow-up, the optical coherence tomography demonstrated inner retinal hyperreflectivity and the fluorescein angiogram showed segmented flow and no neovascularization. On follow-up, the patient had a stable examination with light perception vision and completed antibiotic therapy for bartonella endocarditis. CONCLUSION: The detection of a fatal systemic illness was made promptly with a thorough ocular examination. We highlight the importance of a multidisciplinary approach in making a lifesaving diagnosis.

Teclistamab-Associated Sclerouveitis with Hypopyon.

PURPOSE: To report a case of presumed teclistamab-associated sclerouveitis with hypopyon. METHODS: Case report. RESULTS: A 62-year-old female with relapsed refractory multiple myeloma presented with right eye pain and decreased vision one week after starting teclistamab, and was found to have sclerouveitis with hypopyon. She received intravitreal vancomycin and ceftazidime due to concern for infectious endophthalmitis, but cultures were negative. Systemic workup for infectious and inflammatory etiologies was unremarkable. Her signs and symptoms improved with topical steroids and a one-week pause in teclistamab. This case constituted a Naranjo Adverse Drug Reaction Probability Scale score of 5, representing a "probable" association. CONCLUSION: Teclistamab, a novel bispecific antibody recently approved for the treatment of relapsed or refractory multiple myeloma, may be associated with sclerouveitis with hypopyon.

SH2 domain-containing protein tyrosine phosphatase-2 is enriched in eyelid specimens of rosacea.

Background: Rosacea is a cutaneous disease that may secondarily affect the ocular surface. Due to the vision threatening, cosmetic, psychological, and work productivity impact, the identification of cellular targets that govern rosacea would enhance our understanding of the biology of the disease and delineate targets for therapeutic manipulation. Objective: To characterize the involvement of SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) in the pathogenesis of rosacea. Methods: Specimens from elective ectropion surgery (n = 20) were processed from patients with rosacea (n = 10) and control patients (n = 10). Immunohistochemistry (IHC) and quantitative western blotting (WB) were performed to identify and quantify the presence of SHP2 and 4G10 (a phosphotyrosine antibody) in rosacea compared to normal tissue. IHC samples were graded according to an intensity scale (0-4). Mann-Whitney statistical analyses were performed via a dedicated computerized software package. Results: On WB, SHP2 was expressed in higher concentrations in rosacea specimens (p < 0.05). On IHC, SHP2 was enriched in the epidermis in rosacea (p < 0.05), although 4G10 levels were not statistically significantly different between the two groups (p > 0.05). Conclusions: SHP2 is enriched in cutaneous specimens of rosacea, suggesting a critical role for this protein in the disease and indicating a modifiable therapeutic moiety.

Characteristics of Spontaneously Regressed Retinopathy of Prematurity at Termination of Acute Retinal Screening Examinations Using a Novel Grading System.

PURPOSE: To characterize and compare residual retinal changes of spontaneously regressing retinopathy of prematurity (ROP) at termination of acute-phase retinal screening examinations. METHODS: A retrospective chart review of 521 infants screened for ROP from 2016 to 2019 was performed. Data were collected on patients with at least stage 1 ROP, but who were not treated. The primary outcome measure was presence of residual fibrotic retinal tissue at termination of acute ROP screening examinations. Secondary outcomes included: type of residual fibrotic retinal tissue, persistent avascular retina, vitreous hemorrhage, and retinal detachment. A novel grading system was used to categorize findings. Comparisons between groups were made using Fisher exact tests. RESULTS: A total of 255 eyes met inclusion criteria. A total of 206 of 255 eyes (81%) showed persistent avascular retina, whereas 57 of 255 eyes (22%) showed residual fibrotic retinal tissue at termination of acute screening. All eyes with previous stage 3 ROP showed residual fibrotic retinal tissue (8 of 8 eyes, 100%). Eyes whose highest stage of ROP was stage 2 showed more residual fibrotic retinal tissue at termination of acute screening (40 of 73 eyes, 55%) compared to eyes whose highest stage was stage 1 (9 of 174, 5%) (P < .0001). Stage 3 eyes were excluded from this comparison due to the small sample size. One eye had vitreous hemorrhage at post-menstrual age 44 1/7 weeks. No eyes had retinal detachment. CONCLUSIONS: Despite meeting at least one of the criteria for termination of acute ROP screening, residual fibrotic retinal tissue and persistent avascular retina are common after spontaneous regression of ROP. Further investigation into the long-term clinical significance of these residual changes is warranted. [J Pediatr Ophthalmol Strabismus. 2023;60(5):359-364.].

Sertoli cells require TDP-43 to support spermatogenesis†.

TAR DNA binding protein of 43 kD (TDP-43) is an evolutionarily conserved, ubiquitously expressed transcription factor and RNA-binding protein with major human health relevance. TDP-43 is present in Sertoli and germ cells of the testis and is aberrantly expressed in the sperm of infertile men. Sertoli cells play a key role in spermatogenesis by offering physical and nutritional support to male germ cells. The current study investigated the requirement of TDP-43 in Sertoli cells. Conditional knockout (cKO) of TDP-43 in mouse Sertoli cells caused failure of spermatogenesis and male subfertility. The cKO mice showed decreased testis weight, and low sperm count. Testis showed loss of germ cell layers, presence of vacuoles, and sloughing of round spermatids, suggesting loss of contact with Sertoli cells. Using a biotin tracer, we found that the blood-testis barrier (BTB) was disrupted as early as postnatal day 24 and worsened in adult cKO mice. We noted aberrant expression of the junction proteins connexin-43 (gap junction) and N-cadherin (ectoplasmic specialization). Oil Red O staining showed a decrease in lipid droplets (phagocytic function) in tubule cross-sections, Sertoli cells cytoplasm, and in the lumen of seminiferous tubules of cKO mice. Finally, qRT-PCR showed upregulation of genes involved in the formation and/or maintenance of Sertoli cell junctions as well as in the phagocytic pathway. Sertoli cells require TDP-43 for germ cell attachment, formation and maintenance of BTB, and phagocytic function, thus indicating an essential role for TDP-43 in the maintenance of spermatogenesis.

Risk of corneal epithelial defects with and without postoperative erythromycin ointment after laser photocoagulation for retinopathy of prematurity.

Purpose: We aim to compare the incidence of corneal epithelial defects after laser for retinopathy of prematurity (ROP) with and without the use of postoperative erythromycin ointment. Methods: In this retrospective observational cohort study, a total of 100 infants (200 eyes) consecutively treated with laser for ROP between 2012 and 2018. The primary outcome was presence or absence of corneal epithelial defect using fluorescein on bedside examination within the first week following laser for ROP. Additional data assessed included: the use of postoperative prophylactic erythromycin ointment for 1 week, postoperative day on which examination using fluorescein occurred, presence of corneal opacity, gender, birth weight, and gestation age. The presence or absence of postoperative corneal epithelial defects was compared between eyes receiving postoperative erythromycin ointment or not using a Fisher's exact test. Results: Postoperative corneal epithelial defects were more common in eyes which did not receive postoperative erythromycin (7 of 40 eyes; 17.5%), compared to eyes which did receive erythromycin (1 of 160 eyes; 0.6%; P < 0.0001). Postoperative bedside examinations with fluorescein were performed within 2 days of surgery on 136 of 200 of eyes (68%). Corneal opacities were noted in 3 of 200 eyes (1.5%). Conclusion: We observed less corneal epithelial defects in eyes which received postoperative erythromycin ointment for 1 week after laser for ROP than in those which did not. While multiple variables may influence the presence or absence of postoperative corneal epithelial defects following laser for ROP, consideration for postoperative lubricating ointment following laser for ROP seems reasonable.

Case report: Diffuse metastatic infiltration of the thyroid by esophageal adenocarcinoma mimicking non-neoplastic thyroid disease.

We report a patient who suffered from esophageal cancer that metastasized to the thyroid. There are only a handful of cases of esophageal cancer with metastases to the thyroid reported in the literature. To our knowledge, this is the first with a diffusely infiltrative pattern (the others were focal masses/nodules). This diffusely infiltrative pattern of metastatic disease is important for radiologists to be aware of because it is particularly difficult to detect and is not characteristically neoplastic by pattern. A diffuse parenchymal abnormality that is bilaterally symmetric is more commonly associated with non-neoplastic diffuse thyroid disease, such as autoimmune thyroid diseases (eg, Graves' disease). As such, in addition to the more common non-neoplastic differential diagnoses associated with diffuse thyroid disease, a diffuse thyroid parenchymal abnormality in a patient with a history of esophageal carcinoma should raise the question of diffuse metastatic infiltration.

The acrosomal protein SP-10 (Acrv1) is an ideal marker for staging of the cycle of seminiferous epithelium in the mouse.

The study of spermatogenesis requires accurate identification of the stages of the cycle of the seminiferous epithelium. A stage refers to the unique association of germ cell types at a particular phase of development, as seen in a cross-sectioned seminiferous tubule. Stage-identification, however, is a daunting task. There are 12 stages represented in the mouse seminiferous epithelium. Stages are typically identified on the basis of the morphology of the developing acrosome of spermatids. Although the characteristic features of the acrosome are well-documented in ultrastructure images, a reagent that can highlight the subtle differences in acrosome shape under the light microscope is lacking. Here we demonstrate that a polyclonal antibody raised against the mouse acrosomal protein SP-10 is extremely useful for stage identification. Immunohistochemistry showed that the anti-SP-10 antibody is highly specific for the acrosome of spermatids, as no other cell type in the epithelium showed immunoreactivity. At lower magnification, the gross shape of the acrosome and the increasing intensity of immunostaining served as a guide for the identification of stages I-XII. At higher magnification, characteristic morphological features-such as whether the part of the acrosome that contacts the nuclear surface is round (stage III) or flat (stage IV) or curved (stage VI)-could be identified unambiguously. Overall, we present evidence that SP-10 is a useful marker for staging the cycle of the seminiferous epithelium. The anti-SP-10 antibody works well in different fixatives, on paraffin-embedded as well as cryosections, and has been shown to be useful for characterizing spermatogenic defects in mutant mice.