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.

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.

Use of novel devices for control of intraocular pressure.

This brief review in honor of Douglas Johnson, MD describes the rationales and initial clinical outcomes in studies to date on Trabectome, Glaukos iStent, iScience (canaloplasty), and Solx (suprachoroidal shunt), all newly developed surgical technologies for treatment of open-angle glaucomas. These new approaches to angle surgery have been demonstrated in preliminary case series to safely lower IOP in the mid-teens with far fewer complications than expected with trabeculectomy and without anti-fibrotics. Trabectome and iStent are relatively non-invasive, aim to improve access of aqueous to collector channels and do not preclude subsequent standard surgery. Canaloplasty, modified from viscocanalostomy, is thought to improve trans-trabecular flow. Solx potentially offers an adjustable aqueous outflow into the suprachoroidal space.

Aqueous shunts in glaucoma: a report by the American Academy of Ophthalmology.

OBJECTIVE: To provide an evidence-based summary of commercially available aqueous shunts currently used in substantial numbers (Ahmed [New World Medical, Inc., Rancho Cucamonga, CA], Baerveldt [Advanced Medical Optics, Inc., Santa Ana, CA], Krupin [Eagle Vision, Inc, Memphis, TN], Molteno [Molteno Ophthalmic Ltd., Dunedin, New Zealand]) to control intraocular pressure (IOP) in various glaucomas. METHODS: Seventeen previously published randomized trials, 1 prospective nonrandomized comparative trial, 1 retrospective case-control study, 2 comprehensive literature reviews, and published English language, noncomparative case series and case reports were reviewed and graded for methodologic quality. RESULTS: Aqueous shunts are used primarily after failure of medical, laser, and conventional filtering surgery to treat glaucoma and have been successful in controlling IOP in a variety of glaucomas. The principal long-term complication of anterior chamber tubes is corneal endothelial failure. The most shunt-specific delayed complication is erosion of the tube through overlying conjunctiva. There is a low incidence of this occurring with all shunts currently available, and it occurs most frequently within a few millimeters of the corneoscleral junction after anterior chamber insertion. Erosion of the equatorial plate through the conjunctival surface occurs less frequently. Clinical failure of the various devices over time occurs at a rate of approximately 10% per year, which is approximately the same as the failure rate for trabeculectomy. CONCLUSIONS: Based on level I evidence, aqueous shunts seem to have benefits (IOP control, duration of benefit) comparable with those of trabeculectomy in the management of complex glaucomas (phakic or pseudophakic eyes after prior failed trabeculectomies). Level I evidence indicates that there are no advantages to the adjunctive use of antifibrotic agents or systemic corticosteroids with currently available shunts. Too few high-quality direct comparisons of various available shunts have been published to assess the relative efficacy or complication rates of specific devices beyond the implication that larger-surface-area explants provide more enduring and better IOP control. Long-term follow-up and comparative studies are encouraged.

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.

Corneal thickness measurement in the management of primary open-angle glaucoma: a report by the American Academy of Ophthalmology.

OBJECTIVE: To evaluate published literature to assess whether central corneal thickness (CCT) is a risk factor for the presence, development, or progression of glaucomatous optic nerve damage related to primary open-angle glaucoma (POAG). METHODS: A PubMed literature search limited to English language articles conducted on November 15, 2004 retrieved 195 articles. The authors reviewed these abstracts and selected 57 to review in full text to determine relevance to the assessment questions. A further 24 studies of interest were identified from periodic updates to the literature search, surveillance of the literature, and reference lists of reviewed articles. From the 81 published reports identified, the first author applied specified selection criteria that yielded 37 articles for methodological review because of relevance to the assessment questions. The articles were rated according to the strength of evidence by the panel methodologist. A level I rating was assigned to well-designed properly conducted randomized clinical trials or similar quality-validated cohort studies with appropriate reference standards. A level II rating was assigned to well-designed case-control studies, exploratory cohort studies, and other nonrandomized clinical studies lacking consistently applied reference standards. A level III rating was reserved for poorly designed case-control studies, case series, and papers consisting only of expert opinion without supporting evidence. In addition, each study was graded as positive if it supported a statistical association of CCT with the risk of having or developing glaucomatous optic nerve damage or as negative if no such association was found. RESULTS: There is strong and consistent level I and level II evidence that CCT is a risk factor for progression from ocular hypertension to POAG. Studies that were rated as providing the highest quality of evidence revealed mixed results with respect to glaucoma prevalence. One population-based study (level II) showed a positive association, another larger study (level I) revealed an association of marginal significance, and 3 studies (all level I) found no association of CCT with POAG prevalence. CONCLUSIONS: There is strong evidence that measuring CCT is an important component of a complete ocular examination, particularly for patients being evaluated for the risk of developing POAG. Therefore, CCT measurement should be included in the examination of all patients with ocular hypertension. Although the evidence supporting the necessity of measuring CCT as part of screening for POAG or as a risk factor for glaucoma progression is not as strong, intraocular pressure (IOP) is the only modifiable risk factor in the treatment of glaucoma, and CCT has the potential to significantly impact IOP measurement by applanation tonometry in all patients.

Optic nerve head and retinal nerve fiber layer analysis: a report by the American Academy of Ophthalmology.

OBJECTIVE: To evaluate the current published literature on the use of optic nerve head (ONH) and retinal nerve fiber layer (RNFL) measurement devices in diagnosing open-angle glaucoma and detecting progression. METHODS: A search of peer-reviewed literature was conducted on February 15, 2006 in PubMed and the Cochrane Library for the period January 2003 to February 2006. The search was limited to studies of adults in English-language journals and yielded 442 citations. The panel reviewed the abstracts of these articles and selected 159 articles of possible clinical relevance for review. Of these 159 full-text articles, 82 were determined to be relevant for the first author and methodologist to review and rate according to the quality of evidence. RESULTS: There were no studies classified as having the highest level of evidence (level I). The ONH and RNFL imaging instruments reviewed in this assessment were determined to be highly effective in distinguishing eyes with glaucomatous visual field (VF) loss from normal eyes without VF loss, based on level II evidence. In addition, some studies demonstrated that parameters from ONH or RNFL imaging predicted the development of VF defects among glaucoma suspects. Studies on detecting glaucoma progression showed that although there was often agreement on progression between the structural and functional (VF) tests, a significant proportion of glaucoma patients progressed by either the structural or the functional test alone. CONCLUSIONS: The ONH and RNFL imaging devices provide quantitative information for the clinician. Based on studies that have compared the various available technologies directly, there is no single imaging device that outperforms the others in distinguishing patients with glaucoma from controls. Ongoing advances in imaging and related software, as well as the impracticalities associated with obtaining and assessing optic nerve stereophotographs, have made imaging increasingly important in many practice settings. The information obtained from imaging devices is useful in clinical practice when analyzed in conjunction with other relevant parameters that define glaucoma diagnosis and progression.

Application of second harmonic imaging microscopy to assess structural changes in optic nerve head structure ex vivo.

Glaucoma represents the second leading cause of blindness worldwide. While both age and intraocular pressure (IOP) are well-recognized risk factors for this disease, the underlying pathologic process involves the accelerated death of retinal ganglion cells (RGCs) that is associated with progressive loss of vision. The loss of RGCs has been postulated to occur primarily by injury to axons in the optic nerve head (ONH) due to its anatomic features and the mechanical vulnerability of the lamina cribrosa, the specialized ONH zone comprised of collagen beams that define the channels or pores through which axon bundles exit the eye. Recent advances in multiphoton microscopy using femtosecond lasers that generate second harmonic (SH) signals from collagen allows for direct optical imaging of the lamina cribrosa. We assess the application of SH generated microscopy (SHG) to the study of the ONH, and test the general hypothesis that increasing intraocular pressure in the same eye results in the movement of ONH collagen beams leading to distortion of the lamina cribrosa channels and compression of the axon bundles.

Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma.

PURPOSE: To design an instrument to selectively remove trabecular meshwork and Schlemm's canal inner wall (SCIW), and demonstrate its effectiveness by histologic analysis of treated cadaveric human tissue. METHODS: The design parameters of the instrument were the ability to permanently remove a segment of trabecular meshwork and Schlemm's canal inner wall without causing damage to surrounding tissue, and to allow use with standard anterior segment surgical techniques and equipment via an ab interno approach. Treatment was applied to 20 segments of human corneoscleral rims. The treated areas were examined using a confocal microscope and compared with matching areas in untreated controls and simulated goniotomy. RESULTS: The resultant instrument system surgically removes the trabecular meshwork and Schlemm's canal inner wall from an anterior chamber approach. It consists of a disposable surgical handpiece with irrigation, aspiration, and electrocautery to focally ablate the target tissues. The attached console includes a high-frequency (550 KHz) electrosurgical generator and irrigation/aspiration controlled by a foot pedal. Histologic examination of specimens treated with the Trabectome displayed disruption of the trabecular meshwork and Schlemm's canal inner wall without damage to surrounding structures. The specimens treated by simulated goniotomy displayed significant damage to the outer wall of Schlemm's canal and the surrounding sclera. The controls showed no disruption or damage to any tissues. CONCLUSIONS: The Trabectome system is designed for performing trabeculectomy via an ab interno approach. It successfully removed sections of trabecular meshwork and Schlemm's canal inner wall with less injury to the adjacent tissue compared with goniotomy knife in vitro. Theoretically, this procedure should provide direct access of aqueous humor to Schlemm's canal.

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.

Clinical results with the Trabectome for treatment of open-angle glaucoma.

OBJECTIVE: To describe clinical results from a pilot study of a novel glaucoma surgical device. DESIGN: Prospective interventional case series. PARTICIPANTS: Thirty-seven adult Hispanic and Caucasian patients (17 male, 20 female) with uncontrolled open-angle glaucoma (OAG) in one or both eyes with or without previous surgery or laser treatment were recruited from a clinical practice in Tijuana, Mexico. INTERVENTION: Surgery was performed with the Trabectome (NeoMedix Corp., San Juan Capistrano, CA) in one eye of each patient. MAIN OUTCOME MEASURES: Goldmann applanation intraocular pressures and Snellen visual acuities were measured before and after surgery. Intraoperative and postoperative adverse events were tabulated, and numbers of preoperative and postoperative adjunctive medications were compared before and after surgery. RESULTS: Preoperative pressures after 1 week of medication washout averaged 28.2+/-4.4 mmHg (n = 37). Only 3 patients were not using topical medications preoperatively. Follow-up ranged between 3 months (n = 37) and 13 months (n = 11). Mean postoperative IOPs were 18.4+/-10.9 mmHg (n = 37) at 1 day, 17.5+/-5.9 mmHg (n = 37) at 1 week, 17.4+/-3.5 mmHg (n = 25) at 6 months, and 16.3+/-2.0 mmHg (n = 15) at 12 months. Visions returned to within 2 lines of preoperative levels and remained stable in all patients beyond 3 weeks postoperatively except one, not sutured at surgery, who had a late hyphema probably associated with corneal wound gaping after accidental blunt trauma. The number of adjunctive medications decreased from 1.2+/-0.6 among preoperative patients on medications (n = 34) to 0.4+/-0.6 among all patients at 6 months (n = 25). Blood reflux occurred in all eyes on instrument withdrawal after angle surgery and was present at day 1 in 22 eyes (59%) with clearing by slit-lamp examination at a mean of 6.4+/-4.1 days postoperatively. CONCLUSIONS: The Trabectome seems to offer a safe and effective method of lowering IOP in OAG.

Histopathologic features of conjunctival filtering blebs.

OBJECTIVES: To characterize and compare the histological features of conjunctiva obtained during the repair of trabeculectomy and inadvertent blebs and to assess the effects of antifibrotic agents. METHODS: We used routine paraffin processing and light microscopy to examine conjunctival specimens from 28 eyes undergoing late bleb revision: 19 leaking trabeculectomy blebs, 5 nonleaking trabeculectomy blebs, and 4 inadvertent blebs. Quantitative analysis of histological characteristics included conjunctival epithelial thickness, stromal vascularity, squamous metaplasia, stromal inflammatory cell infiltrate, and goblet cell density. The type of surgery, presence of leaks, prior topical medication, and antifibrotic use were correlated with histological findings. RESULTS: Trabeculectomy blebs (leaking and nonleaking) showed decreases in overall epithelial thickness (P<.02), goblet cell density (P<.001), and vascularity (P<.001) compared with inadvertent bleb controls. Conjunctiva exposed to antifibrotics had fewer layers of epithelial cells than those with no prior exposure (P<.05). CONCLUSIONS: Histological analysis of thin blebs excised following trabeculectomy demonstrated decreases in epithelial thickness and goblet cell density compared with inadvertent blebs. Both leaking and nonleaking trabeculectomy blebs exhibited decreases in localized stromal vascularity and increases in surrounding stromal vascularity compared with normal conjunctiva.

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.

Slit-lamp needle revision for aqueous misdirection after trabeculectomy.

PURPOSE: To describe a slit-lamp needle procedure for the management of aqueous misdirection after trabeculectomy in which more conventional therapies have failed. The pathophysiology of aqueous misdirection and explanation for the efficacy of this procedure are reviewed. METHODS: Two patients in whom aqueous misdirection developed after trabeculectomy refractory to standard medical and laser therapy underwent transcorneal needling to disrupt the anterior vitreous face and reform the anterior chamber. RESULTS: In both cases there was immediate resolution of clinical signs, with normalization of intraocular pressure throughout the 9-month follow-up period. One of the two eyes showed a slow but progressive advance in preexisting peripheral anterior synechia; however, intraocular pressure and axial anterior chamber depth remained normal in both eyes. CONCLUSION: Transcorneal needle disruption of the anterior hyaloid through the peripheral iridectomy was effectively managed two cases of aqueous misdirection. Even if only transiently useful, this simple intervention may serve to minimize corneal damage from iris and lens trauma due to a flat anterior chamber.