Deep Learning Assisted Imaging Methods to Facilitate Access to Ophthalmic Telepathology.

Purpose: To investigate the use of super-resolution imaging techniques to enable telepathology using low-cost commercial cameras. Design: Experimental study. Participants: A total of 139 ophthalmic pathology slides obtained from the Ophthalmic Pathology service at the University of California, Irvine. Methods: Denoising Diffusion Probabilistic Model (DDPM) was developed to predict super-resolution pathology slide images from low-resolution inputs. The model was pretrained using 150 000 images randomly sampled from the ImageNet dataset. Patch aggregation was used to generate large images with DDPM. The performance of DDPM was evaluated against that of generative adversarial networks (GANs) and Robust UNet, which were also trained on the same dataset. Main Outcome Measures: The performance of models trained to generate super-resolution output images from low-resolution input images can be evaluated by using the mean squared error (MSE) and Structural Similarity Index Measure (SSIM), as well as subjective grades provided by expert pathologist graders. Results: In total, our study included 110 training images, 9 validation images, and 20 testing images. The objective performance scores were averaged over patches generated from 20 test images. The DDPM-based approach with pretraining produced the best results, with an MSE score of 1.35e-5 and an SSIM score of 0.8987. A qualitative analysis of super-resolution images was conducted by expert 3 pathologists and 1 expert ophthalmic microscopist, and the average accuracy of identifying the correct ground truth images ranged from 25% to 70% (with an average accuracy of 46.5%) for widefield images and 25% to 60% (with an average accuracy of 38.25%) for individual patches. Conclusions: The DDPM-based approach with pretraining is assessed to be effective at super-resolution prediction for ophthalmic pathology slides both in terms of objective and subjective measures. The proposed methodology is expected to decrease the reliance on costly slide scanners for acquiring high-quality pathology slide images, while also streamlining clinical workflow and expanding the scope of ophthalmic telepathology. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Incidence of Urgent Tube Shunt Surgery for Diabetic Neovascular Glaucoma at a Tertiary Academic Medical Center.

Background: Diabetic neovascular glaucoma is a secondary glaucoma that may require immediate correction of elevated intraocular pressure to control pain and protect the optic nerve. While there is a seasonal trend to glucose levels, it is unknown if a seasonal trend exists for diabetic neovascular glaucoma. Objective: This study evaluates the incidence of urgent glaucoma tube shunt implantation in diabetic neovascular glaucoma in a tertiary academic referral center in Southern California. Methods: Electronic medical records were queried for urgent glaucoma tube shunt surgery from 2014 to 2021. The number of cases were separated by month of occurrence, and average hemoglobin A1c values were calculated per month. Data were analyzed via ANOVA tests and one-tailed t-tests. Results: A total of 127 cases were identified. The months of March and April contained the most cases averaging 3 and 2.75 cases, respectively. April had statistically significant higher case numbers than that of other months (P = .041). ANOVA tests excluding April showed no statistically significant difference between the remaining months (P = .901). Average hemoglobin A1c values were highest in the months of April and March at 9.8 and 9.6%, respectively. Conclusion: Emergency glaucoma tube shunt surgery for diabetic neovascular glaucoma occurs most frequently in April. This observation may provide insight into disease prevention through diabetes management and help improve surgical operations such that staffing and resources are allocated accordingly.

Amyloid Precursor Protein in Abusive Head Trauma Suspects.

PURPOSE: To study orthograde axonal transport with amyloid precursor protein (APP-A4) immunohistochemistry (IHC) in the retina and lamina cribrosa (LC) portion of the optic nerve in abusive head trauma (AHT) suspects. DESIGN: Retrospective, case-control study. METHODS: Seventy-two eyes from suspected AHT victims referred by the Los Angeles Coroner and control eyes from nontraumatized infants were included. IHC was conducted using University of California, Irvine (UCI), Lab Medicine Department's standard protocol and results analyzed by light microcopy after paraffin processing. Quantitation of LC APP-A4 block was estimated in 21 cases with known survival using MetaMorph, a proprietary biomicroscopy imaging software. RESULTS: The presence or absence of APP-A4 label accumulations in retinal ganglion cells, nerve fiber layer at the disc margin, and in LC axonal bundles were compared to matching tissues from nontraumatized control eyes with only background staining. Among the globes from AHT suspects with nerve heads available for study, 94% were positive for LC accumulation of marker. Among suspect AHT cases with known survival after injury of 1 to 1588 days, most demonstrated LC APP-A4 accumulations. CONCLUSIONS: Our findings reinforce a recent publication based on APP-A4 IHC that demonstrated similar orthograde axonal transport block in the LC in children with AHT and recommend that intraocular pressures be recorded and addressed in these patients.

Pediatric coccidioidal orbital granuloma.

PURPOSE: To report a case of orbital coccidiomycosis in an otherwise healthy 11-month-old male. OBSERVATIONS: An 11-month-old male presented to his pediatrician with parental complaints of swelling, erythema, and pain of the right orbit that increased over ten days in the absence of constitutional symptoms. The child's parents reported an earlier fall onto a carpeted floor. After four weeks of conservative treatment and a course of oral cephalexin, he developed a fever, increased erythema, and palpable enlargement of a mass posterior to the lower eyelid. Ultrasound revealed an encysted mass in the inferior orbit, suggestive of an abscess. Urgent ophthalmic referral led to incision and drainage via orbitotomy. Culture, histopathology, and serological testing were positive for Coccidioides spp.. Blood studies revealed mild anemia and thrombocytosis. There was complete resolution of symptoms after surgical drainage and several weeks of oral fluconazole. CONCLUSION AND IMPORTANCE: We describe a patient with orbital coccidiomycosis without apparent systemic involvement, following what was most likely an unrelated minor trauma. Despite being rare, orbital coccidiomycosis should be considered as a primary manifestation of infection when ocular inflammation is encountered, especially in endemic regions.

Combined Epithelial, Stromal, and Anterior Chamber Ingrowth After Penetrating Keratoplasty.

PURPOSE: To present a case of primary graft failure after penetrating keratoplasty found to have epithelial ingrowth into the host stroma on histopathologic analysis. METHODS: This is a single observational case report. RESULTS: We herein describe the clinical course of a case of primary graft failure after penetrating keratoplasty. The corneal button was sent for histopathologic analysis. Analysis of the patient's failed corneal button revealed circumferential epithelial full-thickness wound invasion and stromal epithelial invasion into corneal stroma. CONCLUSIONS: Based on histopathologic analysis and this patient's presentation, the stromal ingrowth followed recipient epithelial invasion of the wound and stromal invasion through clefts in the donor corneal edges. Cases of primary graft failure should be assessed for histopathologic evidence of epithelial stromal ingrowth, despite its rarity. To our knowledge, epithelial ingrowth into the corneal donor stroma after penetrating keratoplasty has not been previously reported.

A novel suprachoroidal microinvasive glaucoma implant: in vivo biocompatibility and biointegration.

BACKGROUND: A major challenge for any glaucoma implant is their ability to provide long-term intraocular pressure lowering efficacy. The formation of a low-permeability fibrous capsule around the device often leads to obstructed drainage channels, which may impair the drainage function of devices. These foreign body-related limitations point to the need to develop biologically inert biomaterials to improve performance in reaching long-term intraocular pressure reduction. The aim of this study was to evaluate in vivo (in rabbits) the ocular biocompatibility and tissue integration of a novel suprachoroidal microinvasive glaucoma implant, MINIject™ (iSTAR Medical, Wavre, Belgium). RESULTS: In two rabbit studies, no biocompatibility issue was induced by the suprachoroidal, ab-externo implantation of the MINIject™ device. Clinical evaluation throughout the 6 post-operative months between the sham and test groups were similar, suggesting most reactions were related to the ab-externo surgical technique used for rabbits, rather than the implant material itself. Histological analysis of ocular tissues at post-operative months 1, 3 and 6 revealed that the implant was well-tolerated and induced only minimal fibroplasia and thus minimal encapsulation around the implant. The microporous structure of the device became rapidly colonized by cells, mostly by macrophages through cell migration, which do not, by their nature, impede the flow of aqueous humor through the device. Time-course analysis showed that once established, pore colonization was stable over time. No fibrosis nor dense connective tissue development were observed within any implant at any time point. The presence of pore colonization may be the process by which encapsulation around the implant is minimized, thus preserving the permeability of the surrounding tissues. No degradation nor structural changes of the implant occurred during the course of both studies. CONCLUSIONS: The novel MINIject™ microinvasive glaucoma implant was well-tolerated in ocular tissues of rabbits, with observance of biointegration, and no biocompatibility issues. Minimal fibrous encapsulation and stable cellular pore colonization provided evidence of preserved drainage properties over time, suggesting that the implant may produce a long-term ability to enhance aqueous outflow.

Eccrine Porocarcinoma: A Rare Tumor of the Eyelid With a Novel Histopathological Finding of Free Tumor Cells in the Tear Film.

The authors present a case of an eyelid eccrine porocarcinoma, a very rare malignant sweat gland tumor characterized histopathologically by nests of atypical poromatous cells and the presence of duct-like lumina. Histopathologic analysis of this case also exhibited numerous loose tumor cells in the adjacent tear film, a finding that has not been previously described.

Clinical and pathological correlation of cotton wool spots in secondary angle closure glaucoma.

PURPOSE: Cotton Wool Spots (CWS) are a commonly described retinal finding in the posterior segment associated with an extensive number of systemic diseases. The appearance of a CWS in the setting of glaucoma has rarely been reported and has not been correlated with pathology to localized loss of the nerve fiber layer previously. In this case report, we augment a previous report of an 18 year old female with a diagnosis of low grade ciliary body melanoma. This patient experienced eventual mechanical angle closure with a CWS appearing in the posterior pole in the setting of acute elevation of intraocular pressure (IOP). This eye underwent enucleation and pathology evaluation. OBSERVATIONS: Fundus photography documented a CWS in the posterior segment during a period of acute elevation in IOP. Subsequently the eye was enucleated due to pain from refractory angle closure glaucoma secondary to low grade iris-ciliary body ring melanoma. The specific site of the prior CWS was studied with 1µ Epon retinal step sections stained with a novel AgNO3 solution. Light microscopy demonstrated a retinal nerve fiber layer scar and inner nuclear layer collapse in the prior location of the CWS. Light microscopy and transmission electron microscopy shortly after enucleation had demonstrated temporal quadrant laminar optic nerve (ON) retrograde axonal transport block. CONCLUSIONS AND IMPORTANCE: Although not commonly associated with glaucoma, CWS can present in the setting of acute elevations of IOP and may be associated with loss of nerve fiber layer. This loss of nerve fiber layer can confound the ability to judge glaucoma progression based on nerve fiber layer thickness via optical coherence tomography and changes in disc contours. Patient care may benefit from care provider's awareness of this possible phenomenon in the setting of angle closure.

Malignant Orbital Meningioma Originating from the Frontal Lobe.

PURPOSE OF THE STUDY: Orbital meningiomas are typically benign tumors, most commonly originating from the dura of the sphenoid wing or the optic nerve sheath. PROCEDURES: We describe an unusual case of a malignant meningioma originating from the frontal lobe that ultimately produced orbital and distant metastases. RESULTS AND CONCLUSIONS: Orbital invasion by the meningioma was preceded by multiple incomplete resections, which may have facilitated access to the orbit. The present case serves to remind clinicians that surgical resection of aggressive, recurrent frontal lobe meningiomas may facilitate subsequent penetration of surrounding structures, particularly by tumors that demonstrate bone-destructive properties.

In Vivo Elasticity Mapping of Posterior Ocular Layers Using Acoustic Radiation Force Optical Coherence Elastography.

Purpose: We used acoustic radiation force optical coherence elastography (ARF-OCE) to map out the elasticity of retinal layers in healthy and diseased in vivo rabbit models for the first time. Methods: A healthy rabbit eye was proptosed and imaged using ARF-OCE, by measuring the tissue deformation after an acoustic force is applied. A diseased retinal inflammation model was used to observe the contrast before and after disease formation. Retinal histologic analysis was performed to identify layers of the retina corresponding with the optical images. Results: The general trend of the retinal layer elasticity is increasing stiffness from the ganglion side to the photoreceptor side, with the stiffest layer being the sclera. In a healthy rabbit model, the mechanical properties varied from 3 to 16 kPa for the five layers that were identified via optical imaging and histology (3.09 ± 0.46, 3.82 ± 0.88, 4.53 ± 0.74, 6.59 ± 2.27, 16.11 ± 5.13 kPa). In the diseased model, we have induced optical damage in a live rabbit and observed a change in the stiffness trend in its retina. Conclusions: High sensitivity elasticity maps can be obtained using the ARF-OCE system to differentiate different retinal layers. Subtle changes in the mechanical properties during the onset of diseases, such as retinal degeneration, can be measured and aid in early clinical diagnosis. This study validates our imaging system for the characterization of retinal elasticity for the detection of retinal diseases in vivo.

An Intractable Case of Prototheca Keratitis and Chronic Endophthalmitis in Stevens-Johnson Syndrome With Boston Type 1 Keratoprosthesis.

PURPOSE: To report a case of recalcitrant Prototheca spp. keratitis and endophthalmitis in a patient with Stevens-Johnson syndrome (SJS) and Boston type 1 keratoprosthesis (B1 KPro). METHODS: Case report. RESULTS: A 67-year-old female with a history of SJS with chronic severe ocular surface disease in her monocular left eye underwent placement of a B1 KPro. Her course was subsequently complicated by persistent Prototheca spp. keratitis and endophthalmitis requiring ongoing treatment with triazole and polyene antifungal agents and multiple surgical revisions of her keratoprosthesis. CONCLUSIONS: Protothecosis is an algal infection that is rarely pathologic in humans, but when present can be difficult to manage. We present the second known case of persistent chronic Prototheca spp. keratitis and endophthalmitis in a patient with long-standing SJS and B1 KPro.

Vascular Steal Syndrome, Optic Neuropathy, and Foreign Body Granuloma Reaction to Onyx-18 Embolization for Congenital Orbito-Facial Vascular Malformation.

A 34-year-old patient presented with a right orbito-facial mass since childhood, consistent with a congenital arteriovenous (AV) malformation. Prior to presentation, she had multiple incomplete surgical resections and embolizations with N-butyl acetyl acrylate and Onyx-18. The patient reported gradual, progressive vision loss shortly after Onyx-18 embolization. Five months after embolization, she presented with decreased vision, disfigurement and mechanical ptosis relating to a large subcutaneous mass affecting the medial right upper eyelid and forehead. Significant exam findings included a visual acuity of 20/400 (20/60 prior to embolization), an afferent pupillary defect, and optic disc pallor. MRI and angiography revealed a persistent AV malformation with feeders from the ophthalmic artery and an absent choroidal flush to the right eye. Pathology from surgical resection showed a significant foreign body giant cell reaction to the embolization material adjacent to the vessels. We suggest that an incomplete embolization with Onyx-18 may have caused vascular steal syndrome from the ophthalmic artery.

Results of Trabectome Surgery Following Failed Glaucoma Tube Shunt Implantation: Cohort Study.

To evaluate the safety and efficacy of Trabectome after failed tube shunt surgery.Twenty patients with prior failed tube shunt surgery who underwent Trabectome alone were included. All patients had at least 3 months of follow-up. Outcomes measured included intraocular pressure (IOP), glaucoma medications, and secondary glaucoma surgeries. The success for Kaplan-Meier survival analysis is defined as IOP ≤21 mm Hg, IOP reduced by at least 20% from preoperative IOP, and no secondary glaucoma surgery.Mean preoperative IOP was 23.7 ± 6.4 mm Hg and mean number of glaucoma medications was 3.2 ± 1.5. At 12 months, IOP was reduced to 15.5 ± 3.2 mm Hg (P = 0.05) and number of medications was reduced to 2.4 ± 1.5 (P = 0.44). Survival rate at 12 months was 84% and 3 patients required additional glaucoma surgery with 15 patients reaching 12 months follow-up. Other than failure of IOP control and transient hypotony (IOP < 3 mm Hg) day 1 in 2 cases, there were no adverse events.Trabecular bypass procedures have traditionally been considered an approach appropriate for early-to-moderate glaucoma; however, our study indicates benefit in refractory glaucoma as well. Eyes that are prone to conjunctival scarring and hypertrophic wound healing, such as those who have failed tube shunt surgery, may benefit from procedures that avoid conjunctival incision such as Trabectome. This study indicates potential benefits in this patient population.Trabectome was safe and effective in reducing IOP at 1-year follow-up in patients with prior failed tube shunt surgery, but not effective in reducing medication reliance in these patients.

New insights into the development of infantile intraocular medulloepithelioma.

PURPOSE: To define the maturational sequence of 3 infantile intraocular medulloepitheliomas. DESIGN: Retrospective clinicohistopathologic and immunohistochemical study. METHODS: Immunoreactivity of paraffin sections for CRX (cone-rod homebox transcription factor) and NeuN (biomarker for neuronal differentiation) were investigated together with other biomarkers, including S100, glial fibrillary acidic protein, epithelial membrane antigen, and various cytokeratins. RESULTS: Three infants (aged 1, 6, and 8 months) had iris neovascularization, 2 had anterior ciliary body tumors, and 1 a posterior tumor associated with a retinochoroidal coloboma. Each tumor displayed a premedullary monolayer of cuboidal epithelium that was S100(+), NeuN(-), and CRX(-) and that transitioned into a multilaminar medullary epithelium forming neurotubules with adluminal cells that were CRX(+). NeuN first appeared in ablumenal neurotubular cells in 1 tumor and was also discovered among neuroblast-appearing cells in another. The third tumor associated with a coloboma was CRX(-) and NeuN(-). CONCLUSIONS: A simple premedullary epithelial monolayer appears to be the fundamental source for the tumor and its multilaminar medullary epithelium. CRX(+) and NeuN(+) cells within the multilayered medullary layer approximate expression patterns similar to those found in retinal development and differentiation. Discovery of these biomarkers in the neoplastic ciliary epithelium in a small number of tumors indicates preliminarily that the most anterior layers of the optic cup have a retained retinal and neuroglial differentiation potentiality. The third case was CRX(-) and NeuN(-) and possibly arose from embryonic pigment epithelium at the edge of the retinochoroidal coloboma. These immunohistochemical findings offer histogenetic and potential diagnostic insights.