Analysis of Prosthetic Replacement of the Ocular Surface Ecosystem Anterior Surface Condition Using Noninvasive Keratograph Break-Up Time.

OBJECTIVES: Noninvasive keratograph break-up time (NIKBUT) was developed as an alternative to fluorescein-based measurements of tear break-up time and may have utility not only for the objective evaluation of tear film stability on the corneal surface but also on the surface of scleral and contacts lenses. We report on two cases that highlight the potential use of NIKBUT to provide objective prelens tear film stability data to evaluate the anterior surface of a customized ocular surface prosthetic devices (PD; PROSE, BostonSight, Needham, MA). METHODS: Case report and literature review. RESULTS: Case 1 demonstrates improvement in prelens tear film stability with NIKBUT increasing from 4.59 to 11.47 sec after the addition of a polyethylene glycol-based polymer coating to the PD surface. In case 2, when a NIKBUT value could not be obtained, keratograph infrared images were used to evaluate improved anterior lens surface wetting. CONCLUSION: Noninvasive keratograph break-up time may provide an objective modality to evaluate prelens tear film stability and PD wettability. Such measurements may allow for a better understanding of visual degradation related to PD lens condition and the appropriate timing of lens recoating, reconditioning, and replacement.

Case report: Concomitant use of nightly vitamin A ointment with daily PROSE wear for ocular surface disease associated with chronic Stevens-Johnson syndrome.

Purpose: To describe a case of chronic ocular surface disease associated with Stevens-Johnson Syndrome (SJS) in which the addition of nightly topical ophthalmic preservative free vitamin A ointment to the daily use of a customized ocular surface prosthetic device (PROSE) appears to mitigate disease progression. Observations: A 51-year-old female with SJS secondary to lamotrigine use presented for follow up evaluation. Ocular history was significant for acute SJS twenty-four years prior with chronic ocular surface sequelae predominantly affecting the left eye. The condition had been stabilized without progression by utilizing long term PROSE daytime wear along with nightly application of topical ophthalmic vitamin A ointment. The patient reported non-compliance with vitamin A ointment use for the prior three months. The ocular surface examination of the left eye was notable for significantly progressed inferior keratinization and neovascularization which had been unchanged over the course of the three prior annual exams. After restarting nightly topical ophthalmic vitamin A ointment and continuing regular PROSE use, there was no further ocular surface disease progression in the ensuing 4 years of follow up. Conclusion and Importance: The use of nightly topical ophthalmic vitamin A ointment may be a viable adjuvant therapy alongside daily PROSE use for progressive chronic SJS ocular surface disease.

Case report: Utilization of a scleral lens to mitigate exposure keratopathy and associated mental health decline.

PURPOSE: To report a case of acute exposure keratopathy with comorbid depression and improvement of both conditions with the use of a scleral lens (SL). OBSERVATIONS: A 72-year-old male with a past ocular history significant for extensive basal cell carcinoma (BCC) excision of the right upper and lower eyelids presented for evaluation of exposure keratitis and consideration of a SL for the right eye. Examination was notable for post-surgical irregular lid margins with lagophthalmos, trichiasis and an Oxford Grade I staining of the central exposed cornea. Medical history was notable for chronic severe depression and anxiety with suicidal ideation. Upon treatment with a SL, the patient noted ocular comfort, and reported significantly improved affect. CONCLUSION AND IMPORTANCE: Currently, there is no peer reviewed literature reporting on the management of exposure keratopathy in the setting of comorbid affective disorders. This case highlights the improvement in quality of life for a patient with exposure keratitis and severe depression with suicidal ideation and points to the potential utilization of a SL to mitigate the risk of mental health decompensation.

Early Postoperative Therapeutic Scleral Lens Intervention for Penetrating Keratoplasty Complications in Atopic Keratoconjunctivitis.

ABSTRACT: A 52-year-old white man with keratoconus and severe atopic keratoconjunctivitis underwent penetrating keratoplasty (PK) for visual rehabilitation in the left eye. Post-PK complications included a persistent epithelial defect. Therapeutic scleral lens wear was initiated 2 weeks post-PK. Customizations were incorporated into the lens design to prevent suction and corneal hypoxia during lens wear. Post-PK herpes epithelial keratitis developed shortly thereafter, causing recurrence of a nonhealing epithelial defect. The patient was treated with oral antiviral therapy, discontinuation of dupilumab, and daily waking-hour scleral lens wear, which was used as an antibiotic drug delivery device. The cornea fully epithelialized, and best-corrected visual acuity improved to 20/40-2. The patient continued with daily waking-hour scleral lens wear and was without recurrence of persistent epithelial defect or herpes keratitis at 18 months. No scleral lens-related complications were observed despite the unconventional early intervention with a therapeutic scleral lens.

Treatment and Management of Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome With Scleral Prosthetic Devices.

ABSTRACT: This case report highlights the unique application and long-term benefits of customized scleral devices in a patient with ocular complications from ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome over the span of 10 years. A 13-year-old girl with a history of EEC syndrome and ocular manifestations, including severe bilateral dry eye disease, corneal neovascularization and scarring, progressive fibrous pannus, and limbal stem cell deficiency, was examined and fitted with scleral devices. The goal of treatment was to stabilize the ocular surface, enhance vision, and improve ocular comfort. Throughout the course of treatment, there was minimal progression in ocular signs, despite interruptions in scleral device wear from application and removal challenges secondary to ectrodactyly. Customized scleral devices provided an optimal environment to support the ocular surface, improve comfort, and improve visual acuity. Further studies are required to demonstrate the benefits of scleral devices in larger populations of patients with EEC syndrome.

Case report: Utilization of neutral density filters for densitometry analysis of dense corneal opacities.

Purpose: This report describes the technique of utilizing a neutral density filter (NDF) during Scheimpflug imaging of a dense corneal opacity in order to increase data acquisition success and improve data reliability for densitometry analysis. Observations: A 49-year-old female with Steven-Johnson Syndrome secondary to sulfonamide use presented for routine follow up evaluation of her customized ocular surface prosthetic device (PD). Her ocular history was significant for mucous membrane grafting and limbal stem cell transplant in both eyes. The ocular surface examination of the left eye was notable for chronic dense neovascularization and scarring of the temporal and inferior cornea which extended into the visual axis. Scheimpflug imaging and densitometry analysis were performed in order to quantify the severity of the scar, however, there was significant difficulty in acquiring densitometry data. During a subsequent follow-up visit to monitor the scar, standardized room lighting and a neutral density filter were used to obtain reproducible and reliable imaging for densitometry analysis. The corneal scar was monitored over time using this standardized imaging protocol and by densitometry analysis minimal progression of the scar was evident, suggesting that recently documented significant vision loss in the left eye could not be attributed solely to changes in the scar. Conclusion and Importance: The use of a neutral density filter along with standardized ambient lighting conditions when performing Scheimpflug imaging may be necessary to reliably monitor densitometry progression of clinically severe corneal opacities.

Ocular Graft-versus-Host Disease Underdiagnosis: A Survey Study.

Purpose: To understand the degree and explore the possible causes of ocular graft-versus-host disease (oGVHD) underdiagnosis in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and Methods: A 15-question survey was emailed to 6032 subscribers to the Blood and Marrow Transplant Information Network. A total of 371 respondents confirmed the history of allo-HSCT, of which 335 were symptomatic. Their self-reported symptoms, onset, treatments tried, degree of symptom control and established diagnoses of systemic chronic graft-versus-host disease (cGVHD) and oGVHD were analyzed. Results: Among the 335 symptomatic survey respondents, 306 reported their ocular symptom onset was after allo-HSCT, with only 170 [55.6% (170/306)] ever receiving a diagnosis of oGVHD; 23 reported worsening pre-existing ocular symptoms after allo-HSCT, with only 5 [21.7% (5/23)] ever receiving a diagnosis of oGVHD; 6 reported stable symptoms before and after allo-HSCT, with 1 ever receiving a diagnosis of oGVHD. Of the 176 respondents carrying the diagnosis of oGVHD, 167 [94.9% (167/176)] also had the diagnosis of cGVHD. Logistic regression analysis showed that the diagnosis of oGVHD was highly correlated with the number of symptoms and treatments one reported. Furthermore, 35% of the respondents with new onset ocular symptoms reported onset within the first 6 months after allo-HSCT (previously reported), as well as 39% of the respondents with worsened existing symptoms. Conclusion: oGVHD underdiagnosis is likely associated with the previous diagnostic criteria, in which cGVHD of another organ system was required. The correct notion that oGVHD commonly causes severe dry eye disease has likely led to its underdiagnosis in patients with fewer number of symptoms and/or who tried fewer treatments.

Case Report: Novel Patient Training Technique for the Application and Removal of Scleral Lenses.

SIGNIFICANCE: This report shares a technique that can be used to assist training patients to properly and safely apply and remove prosthetic replacement of the ocular surface ecosystem devices (PD) or scleral lenses to reduce patient training nervousness, limit adverse events from training, and limit training failures. PURPOSE: This study aimed to introduce a novel scleral lens application and removal training method. CASE REPORT: A 28-year-old woman with limbal stem cell deficiency secondary to contact lens overwear in the left eye greater than the right eye presented for prosthetic replacement of the ocular surface ecosystem treatment. Her ocular history included herpes simplex keratitis, fungal keratitis, and acanthamoeba keratitis in the left eye, which ultimately resulted in corneal perforation requiring repair with cyanoacrylate adhesive. The patient was initially fitted with a PD in 2015 in the left eye but had difficulty with application of the device on the eye, which resulted in discontinuation of use. She returned to the clinic in 2021 for a reevaluation and PD refitting. To address her past difficulties surrounding application and removal of the device, a novel piggyback technique (applying a second scleral lens on top of the primary customized scleral lens that is already on the eye) was used to successfully train the patient. CONCLUSIONS: A novel piggyback training technique can be used to overcome obstacles during the scleral lens application and removal training process.

OSDI Outcomes Based on Patient Demographic and Wear Patterns in Prosthetic Replacement of the Ocular Surface Ecosystem.

PURPOSE: To evaluate the impact of prosthetic replacement of the ocular surface ecosystem (BostonSight PROSE) treatment on symptom outcomes based on the Ocular Surface Disease Index (OSDI). PATIENTS AND METHODS: This was a single-center, retrospective analysis of consecutive patients who initiated PROSE treatment between September 2017 and December 2019 by the same clinician. The primary outcome measure was to compare OSDI survey scores at baseline prior to PROSE treatment and at follow-up, after PROSE treatment. Indication for treatment, sex, age, device diameter, average wear time, preexisting mental illness, duration of PROSE wear, and status of PROSE wear at follow-up were also studied. RESULTS: A total of 134 patients underwent PROSE treatment and completed a baseline OSDI survey during the study period. Forty-three patients completed a follow-up OSDI survey and were included in the study analysis. The most common treatment indications were keratoconjunctivitis sicca (n=27) and corneal ectasia (n=16). Baseline average OSDI score was 56.9±23.7 for the 43 subjects who completed a subsequent OSDI survey. The last documented average follow-up OSDI for those 43 subjects was 23.8±15.6, median (IQR) of 22.9 (10.4 to 32.3), and a statistically significant 54.7±27.6% average improvement from baseline (p<0.01). All patients, except for two, showed improvement in OSDI score. Statistically significant improvement occurred regardless of underlying diagnosis with no statistically significant difference based on age, sex, mental illness, or device diameter and no statistical correlation with average wear time, or duration of PROSE wear. CONCLUSION: PROSE treatment improves visual function and symptom relief as demonstrated by the OSDI survey. Sex, age, preexisting mental illness, device diameter, average wear time, and duration of wear had no statistically significant impact on OSDI outcomes.

Scleral Tonometry Precision During Scleral Lens Wear: A Pilot Study.

PURPOSE: To evaluate the reproducibility, and therefore the utility, of using traditional tonometry devices for measuring intraocular pressure (IOP), while a prosthetic replacement of the ocular surface ecosystem device (PD) or scleral lens is applied to the eye. PATIENTS AND METHODS: Twenty subjects (40 eyes) with keratoconus were enrolled. With PD applied, the first 10 consecutive patients had IOP measured multiple times with a handheld tonometer (Tono-Pen AVIA, Reichert, Depew, NY) on the superotemporal sclera 1 mm posterior to the PD edge. This identical procedure was repeated for the next 10 consecutive patients with a pneumatonometer (Model 30, Reichert, Depew, NY). Once three reliable measurements, as defined by the study protocol, were obtained for an eye, the procedure was repeated with the same tonometer device on the fellow eye. RESULTS: The mean standard deviation for reliable IOP measurements was ±2.92 mmHg, median (IQR) of 2.62 (1.68 to 3.53) mmHg in the handheld tonometer group and ±1.98 mmHg in the pneumatonometer group. There was no statistically significant difference between the groups (p = 0.07). The mean IOP range for the reliable IOP measurements was 5.5 ± 3.80 mmHg, median (IQR) of 5 (3 to 7) mmHg for the handheld tonometer group and 3.71 ±1.12 mmHg in the pneumatonometer group. There was no statistically significant difference between the groups (p = 0.06). CONCLUSION: Handheld tonometry and pneumatonometry have poor reproducibility when used to measure scleral IOP in keratoconus patients, while a PD is applied to the eye. An alternative research model and methodology should be investigated and confirmed to have precision prior to proceeding with further analysis of any relationship between scleral lens wear and IOP.

Scleral Lens and Prosthetic Replacement of the Ocular Surface Ecosystem Utilization in Ocular Graft-versus-Host Disease: A Survey Study.

PURPOSE: To evaluate the utilization of scleral lenses and prosthetic replacement of the ocular surface ecosystem devices (SL/PDs) in the management of ocular graft-versus-host disease (oGVHD). PATIENTS AND METHODS: A survey of 15 questions was sent via email to 6032 subjects registered with the Blood and Marrow Transplant Information Network. The survey reviewed transplant history, graft-versus-host disease history, as well as oGVHD symptoms and onset. Additional questions surveyed treatments used for oGVHD, as well as the degree of ocular symptom control and experience with SL/PDs. A total of 306 respondents met the eligibility requirements to be part of the analyzed cohort. RESULTS: The mean number of symptoms reported from the analyzed cohort was 4.79 ± 2.44, median (IQR) of 5.0 (3.0 to 7.0), with the most common symptom being gritty, dry eyes (87%). The mean number of treatments utilized across the analyzed cohort was 3.21 ± 2.55, median (IQR) of 2.5 (1.0 to 5.0), with the most common treatment being artificial tears (86%). Wearing scleral lenses resulted in a mean of 5.42 ± 1.86, median (IQR) of 6.0 (4.0 to 7.0) symptoms improving, with improved dryness/grittiness of the eyes (94%), improved eye pain (92%) and improved quality of life (89%) being the most commonly improved symptoms. Fifty-six percent of those wearing scleral lenses wished the lenses had been recommended sooner. The most common reason patients cited for not wearing scleral lenses was that they had never heard of them (63%). CONCLUSION: SL/PDs help to control the symptoms of oGVHD. With their use, clinicians are able to improve the quality of life of this patient population. Despite the known benefits, SL/PDs still remain underutilized in oGVHD care. A majority of current SL/PD wearers wish that they had been recommended sooner as a treatment option. SL/PDs should be considered a component of comprehensive oGVHD management.

Case Report: Use of Prosthetic Replacement of the Ocular Surface Ecosystem Treatment of Traumatic Lid Ptosis in a Pediatric Patient.

SIGNIFICANCE: This report shares the long-term outcomes of an uncommon use of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment and scleral lenses in the treatment for patients with ptosis who are not surgical candidates. PURPOSE: This study aimed to describe a case of pediatric traumatic lid ptosis and follow-up during an 8-year period with PROSE treatment. CASE REPORT: A 7-year-old Honduran girl presented with a history of severe cranial, facial, and ocular trauma as a result of a motor vehicle accident. Significant ptosis with left-sided facial paralysis and irregular astigmatism significantly reduced the patient's visual function in the left eye. She was evaluated and treated with a scleral prosthetic device in the left eye to improve vision, the ocular surface, and overall function for activities of daily living. After 8 years of PROSE treatment, acuity in the left eye remained stable at 20/25. The corneal health remained stable throughout this period, without complications of corneal neovascularization or corneal edema. CONCLUSIONS: Prosthetic replacement of the ocular surface ecosystem treatment provided support of the ocular surface and mechanical left upper eyelid lift in a traumatic eyelid ptosis, ultimately providing improved visual function during an extensive 8-year period in a pediatric patient. Further studies are needed to evaluate the applicability of this approach in broader ptosis cases.

Self-Retained Cryopreserved Amniotic Membrane for the Management of Corneal Ulcers.

PURPOSE: To evaluate the clinical outcomes of self-retained cryopreserved amniotic membrane (cAM) for the treatment of corneal ulcers. METHODS: This was a single-center, retrospective review of consecutive patients with non-healing corneal ulcers that underwent treatment with self-retained cAM (PROKERA® Slim). The primary outcome measure was time to complete corneal epithelialization. Ocular discomfort, corneal staining, corneal signs, and visual acuity were assessed at 1 week, 1 month, 3 months, and 6 months. Complications, adverse events, and ulcer recurrence were also recorded. RESULTS: A total of 13 eyes (13 patients) with recalcitrant corneal ulcers were included for analysis, 9 (69%) of which progressed from neurotrophic keratitis (NK). Prior to cAM application, patients used conventional treatments such as artificial tears (n = 11), antibiotics (n = 11), ointment (n = 11), steroids (n = 6), and antivirals (n = 3). Self-retained cAMs (n = 1.5 ± 0.8) were placed for 6.8 ± 3.4 days, during which time antibiotics were continued. Four cases (31%) were subsequently treated with bandage contact lens (n = 3) and tarsorrhaphy (n = 1). All corneal ulcers healed in a median of 14 days (range: 4-43). This was accompanied by a significant improvement in ocular discomfort, corneal staining, and corneal signs at 1 week, 1 month, 3 months, and 6 months (P<.05). Recurrence was noted in one case. No adverse events were observed. CONCLUSION: Self-retained cAM may be a valuable, in-office treatment option for healing recalcitrant corneal ulcers of various etiologies, especially those with underlying NK. Further prospective, controlled studies are warranted.

Videokeratography in conductive keratoplasty.

PURPOSE: We used EyeSys videokeratography to evaluate corneal shape changes induced by conductive keratoplasty, a procedure that utilizes radio frequency energy to alter corneal shape to correct hyperopia. METHODS: Follow-up data were available for 19 eyes (out of 24 eyes of 13 patients). Preoperative spherical hyperopia ranged from +0.75 to +3.25 D with astigmatism <0.75 D. Manifest refractive spherical equivalent refraction (MRSE), uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), topographical parameter predicted corneal acuity (PCA), corneal uniformity index (CU Index), regular astigmatism, total astigmatism, average simulated keratometry (Avg Sim K), effective refractive power, and asphericity were measured preoperatively and at 6 and 12 months postoperatively. RESULTS: Twelve months postoperatively, mean PCA, CU Index, and BSCVA were maintained at preoperative levels. Mean UCVA (LogMAR) improved from 0.53+/-0.21 to 0.10+/-0.19 (P<.05) with a mean MRSE change from +1.62+/-0.76 D to -0.06+/-0.84 D (P<.05) from preoperative to 12 months postoperative. Mean asphericity increased +0.044+/-0.24 D (P>.05), mean Avg Sim K increased 1.88+/-0.72 D (P<.05), mean effective refractive power increased 1.71+/-0.79 D (P<.05), mean cylinder (cycloplegic refraction) increased 0.19+/-0.36 D (P<.05), mean regular astigmatism increased 0.25+/-0.49 D (P>.05), and mean irregular astigmatism decreased 0.01+/-0.13 D (P>.05) from preoperative to 12 months after conductive keratoplasty. CONCLUSIONS: Avg Sim K and effective refractive power changes support the refractive results; 12-month postoperative maintenance of BSCVA, PCA, and CU Index suggest the procedure is safe. Conductive keratoplasty induced a slight regular astigmatism in some eyes, which decreased with time. The increase in mean corneal asphericity indicated possible induction of central and peripheral cornea changes.

Calpain regulates enterocyte brush border actin assembly and pathogenic Escherichia coli-mediated effacement.

This study identifies calpain as being instrumental for brush border (BB) microvillus assembly during differentiation and effacement during bacterial pathogenesis. Calpain activity is decreased by 25-80% in Caco 2 lines stably overexpressing calpastatin, the physiological inhibitor of calpain, and the effect is proportional to the calpastatin/calpain ratio. These lines exhibit a 2.5-fold reduction in the rate of microvillus extension. Apical microvillus assembly is reduced by up to 50%, as measured by quantitative fluorometric microscopy (QFM) of ezrin, indicating that calpain recruits ezrin to BB microvilli. Calpain inhibitors ZLLYCHN2, MDL 28170, and PD 150606 block BB assembly and ezrin recruitment to the BB. The HIV protease inhibitor ritonavir, which inhibits calpain at clinically relevant concentrations, also blocks BB assembly, whereas cathepsin and proteasome inhibitors do not. Microvillus effacement is inhibited after exposure of calpastatin-overexpressing cells to enteropathogenic Escherichia coli. These results suggest that calpain regulates BB assembly as well as pathological effacement, and indicate that it is an important regulator involved in HIV protease inhibitor toxicity and host-microbial pathogen interactions.