Recognizing vitamin A deficiency: special considerations in low-prevalence areas.

PURPOSE OF REVIEW: Although vitamin A deficiency (VAD) is rare in well resourced countries, there is a growing trend of VAD in at-risk pediatric populations. Early diagnosis is critically important to prevent its associated morbidity and mortality. This review highlights key lessons for evaluation, diagnosis, and management of children with xerophthalmia in the United States. It synthesizes the latest findings from the literature on the pathophysiology, epidemiology, risk factors, evaluation, and management of VAD in low-prevalence areas. RECENT FINDINGS: Vitamin A is crucial for maintaining the functional integrity of the eye, immune system, skin, and mucous membranes. Despite the scarcity of VAD in developed countries, there are increasing reports of VAD in at-risk children, including those with autism spectrum disorder and gastrointestinal conditions. There is a broad range of manifestations of VAD, posing a diagnostic challenge. Familiarity with the variable presentations of VAD and having a high index of suspicion in at-risk populations can aid in its early diagnosis. Systemic vitamin A supplementation and a multidisciplinary approach are important components of the management of VAD. SUMMARY: Even in well resourced countries, VAD should remain on the differential in patients with risk factors who present with relevant signs and symptoms. Early diagnosis and appropriate involvement of a multidisciplinary care team can help prevent morbidity and mortality associated with VAD.

Herpes Zoster Chorioretinopathy: A Case Series.

PURPOSE: To report two patients with herpetic zoster panuveitis and chorioretinopathy with choroidal hypopigmentation. METHODS: Retrospective chart review of two patients. RESULTS: We report a series of two patients with a history of HZO with orbital inflammation and panuveitis, who developed patchy choroidal depigmentation consistent with a choroidopathy. The lesions were extensive and involved the posterior pole and mid-periphery in both cases. Both cases demonstrated scattered areas of ellipsoid zone loss, and fluorescein angiography showed corresponding late hyperfluorescence. OCTA in one case demonstrated flow voids at the level of choriocapillaris. CONCLUSIONS: Our series suggests that herpetic chorioretinopathy may be a relatively benign process that presents late and may involve large areas of the posterior choroid.

Treatment Outcomes of Intravitreal Aflibercept for Uveitic Macular Edema.

BACKGROUND/AIMS: To evaluate the efficacy of intravitreal aflibercept for UME (uveitic macular). METHODS: A retrospective review of records of patients that received aflibercept for UME from January 2017 to August 2022 was conducted. The primary outcomes were mean change in visual acuity (VA) and central subfield thickness (CST) 6 and 12 months from the start of aflibercept treatment. RESULTS: A total of 16 eyes of 12 patients were included. Indications for treatment included eyes that had previously demonstrated a history of elevated intraocular pressure secondary to a steroid response (n = 10) or a history of non-response or partial response to local corticosteroids (n = 6). Fifteen eyes (94%) demonstrated a reduction in CST after their initial injection. At 6-months, mean VA gain was 2.6 ± 7.7 letters (p = 0.24) from a mean VA of 67.8 ± 10.7 letters at baseline and mean CST improved by 97.6 ± 113.5 µm (p = 0.004) from 458.6 ± 123.1 µm at baseline. Fourteen eyes had 12-months of follow up and received a median of 4 injections over 12 visits. The mean VA at 12-months remained stable compared to baseline (mean change of -1.4 ± 12.5 letters (p = 0.87)) while the CST improved by a mean of 90.9 ± 114.6 µm (p = 0.053) compared to baseline. CONCLUSION: Intravitreal aflibercept injections resulted in reduced central subfield thickness at all time-points. It appears to be an effective treatment alternative for UME, particularly for patients who are not responsive to local corticosteroids or who have contraindications to corticosteroid treatment.

Indocyanine Green Angiography of Optic Disc Granuloma in Ocular Sarcoidosis.

PURPOSE: To report novel indocyanine green angiography (ICG) findings of optic disc granulomas secondary to sarcoidosis. METHODS: Observational case report. RESULTS: A 36-year-old white male, who had previously been evaluated for birdshot chorioretinopathy and tested HLA-A29 negative, was referred for evaluation of choroidal lesions in both eyes. Fundus examination revealed ovoid choroidal lesions bilaterally in the posterior pole. Optical coherence tomography demonstrated bilateral focal choroidal elevations in the posterior pole and optic discs consistent with granulomas. ICG revealed diffuse choroidal hypocyanescent spots with late-phase focal hypercyanescence of the optic discs in both eyes corresponding to the granulomas. After three months of prednisone and immunomodulatory treatment, the granulomas improved and the optic disc hypercyanescence resolved. CONCLUSION: We describe a case of ocular sarcoidosis mimicking birdshot-like lesions, and ICG findings revealed late hypercyanescence, which resolved with treatment.

C-DU(KE) Calculator: A Clinical Tool for Risk Stratification in Infectious Keratitis.

PURPOSE: The aim of this study was to identify characteristics of infectious keratitis predictive of poor outcome to develop a web-based predictive calculator. METHOD: A retrospective chart review was performed at the Duke Eye Center. Two hundred fifteen adult patients with culture-proven infectious keratitis presenting between January 1, 2016, and December 31, 2020, were separated into a derivation set (136 patients, 53 positives; 83 controls) and a temporal validation set (79 patients, 26 positives; 53 controls). The poor outcome group consisted of patients requiring penetrating keratoplasty for visually significant scarring, penetrating keratoplasty for ulcer progression, or evisceration/enucleation for endophthalmitis. Univariable analysis was performed followed by stepwise multivariable logistic regression to obtain a predictive model in the derivation data set. Culture-naïve and postculture models were constructed. Discrimination and calibration were assessed using the area under the curve (AUC) and calibration plots, respectively. RESULTS: The culture-naïve model consisted of corticosteroid drop use postsymptom onset [Odds Ratio (OR) = 2.3, P = 0.054], decreased vision (OR = 2.4, P = 0.001), and increased ulcer area (OR = 1.017, P = 0.017). The postculture model additionally included fungal keratitis (OR = 5.4, P = 0.006) and elapsed time from symptoms to organism-sensitive therapy (OR = 1.027, P = 0.014). The models were summarized by the acronym C-DU(KE). The AUCs for the culture-naïve model were 0.794 in the derivation set and 0.850 in the validation set. The AUCs for the postculture model were 0.898 in the derivation set and 0.946 in the validation set. Calibration plots indicated goodness of fit in the data sets for both models. The calculator was deployed under the URL: https://duke-eye-calculator.shinyapps.io/Corneal_Ulcers/ . CONCLUSIONS: The C-DU(KE) calculator permits a data-driven prediction of outcome in infectious keratitis that can supplement clinical judgment.

Increasing Rates of Herpes Zoster Ophthalmicus and the COVID-19 Pandemic.

Purpose: This epidemiologic study evaluates the variance in incidence of Herpes Zoster (HZ) and Herpes Zoster Ophthalmicus (HZO) within a single healthcare system with an aim to analyze their relationship to the COVID-19 pandemic. Methods: All patients attending the Duke University Health System (DUHS) from January 1, 2018, to December 31, 2021, were included. General and COVID-related trends of HZO and HZ were analyzed based on new ICD-9 or ICD-10 diagnosis codes, compared with the total number of patients seen at DUHS during this period, and the number of reported COVID-19 cases in North Carolina obtained using the CDC data tracker. Results: This study included 16,287 cases of HZ of whom 1,294 (7.94%) presented with HZO. The overall incidence of HZO showed an average yearly increase of 5.6%, however HZ incidence decreased by 5.3% per year. When comparing incidence rates of HZO in the 12-months before and after the COVID-19 pandemic onset in the United States (March 2020), the average incidence from March 2020 to February 2021 was 27.6 ± 11.6 compared to 18.0 ± 2.7 from March 2019 to February 2020 (p = 0.01). Moreover, 10/12 (83.3%) of the months had a higher incidence rate of HZO in the post-COVID onset year compared to their corresponding month in the pre-COVID year. Conclusion: The results show HZO incidence may be increasing, despite an overall lower HZ incidence. This could suggest a distinct mechanism for HZO appearance. The COVID pandemic, directly or indirectly, may have accelerated the already increasing HZO incidence.

Open-Source Automated Segmentation of Neuronal Structures in Corneal Confocal Microscopy Images of the Subbasal Nerve Plexus With Accuracy on Par With Human Segmentation.

PURPOSE: The aim of this study was to perform automated segmentation of corneal nerves and other structures in corneal confocal microscopy (CCM) images of the subbasal nerve plexus (SNP) in eyes with ocular surface diseases (OSDs). METHODS: A deep learning-based 2-stage algorithm was designed to perform segmentation of SNP features. In the first stage, to address applanation artifacts, a generative adversarial network-enabled deep network was constructed to identify 3 neighboring corneal layers on each CCM image: epithelium, SNP, and stroma. This network was trained/validated on 470 images of each layer from 73 individuals. The segmented SNP regions were further classified in the second stage by another deep network as follows: background, nerve, neuroma, and immune cells. Twenty-one-fold cross-validation was used to assess the performance of the overall algorithm on a separate data set of 207 manually segmented SNP images from 43 patients with OSD. RESULTS: For the background, nerve, neuroma, and immune cell classes, the Dice similarity coefficients of the proposed automatic method were 0.992, 0.814, 0.748, and 0.736, respectively. The performance metrics for automatic segmentations were statistically better or equal as compared to human segmentation. In addition, the resulting clinical metrics had good to excellent intraclass correlation coefficients between automatic and human segmentations. CONCLUSIONS: The proposed automatic method can reliably segment potential CCM biomarkers of OSD onset and progression with accuracy on par with human gradings in real clinical data, which frequently exhibited image acquisition artifacts. To facilitate future studies on OSD, we made our data set and algorithms freely available online as an open-source software package.

Meibomian Gland Dysfunction: A Route of Ocular Graft-Versus-Host Disease Progression That Drives a Vicious Cycle of Ocular Surface Inflammatory Damage.

PURPOSE: To investigate the role of aggressive meibomian gland dysfunction (MGD) in the immune pathogenesis of ocular graft-vs-host disease (GVHD). METHODS: In mice, an allogeneic GVHD model was established by transferring bone marrow (BM) and purified splenic T cells from C57BL/6J mice into irradiated C3-SW.H2b mice (BM+T). Control groups received BM only. Mice were scored clinically across the post-transplantation period. MGD severity was categorized using the degree of atrophy on harvested lids. Immune disease was analyzed using flow cytometry of tissues along with fluorescent tracking of BM cells onto the ocular surface. In humans, parameters from 57 patients with ocular GVHD presenting to the Duke Eye Center were retrospectively reviewed. MGD was categorized using the degree of atrophy on meibographs. Immune analysis was done using high-parameter flow cytometry on tear samples. RESULTS: Compared with BM only, BM+T mice had higher systemic disease scores that correlated with tear fluid loss and eyelid edema. BM+T had higher immune cell infiltration in the ocular tissues and higher CD4+-cell cytokine expression in draining lymph nodes. BM+T mice with worse MGD scores had significantly worse corneal staining. In patients with ocular GVHD, 96% had other organs affected. Patients with ocular GVHD had abnormal parameters on dry eye testing, high matrix metalloproteinase-9 positivity (92%), and abundance of immune cells in tear samples. Ocular surface disease signs were worse in patients with higher MGD severity scores. CONCLUSIONS: Ocular GVHD is driven by a systemic, T-cell-dependent process that causes meibomian gland damage and induces a robust form of ocular surface disease that correlates with MGD severity. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Bilateral Exudative Retinal Detachments and Panuveitis in a Patient with Multiple Myeloma.

PURPOSE: To report a case of bilateral exudative retinal detachments and panuveitis in a patient with multiple myeloma (MM). CASE REPORT: A 54-year-old patient with non-proliferative diabetic retinopathy was referred with blurred vision and scotomas in both eyes (OU). Three months prior to the onset of ocular symptoms, he was diagnosed with systemic MM and was receiving chemotherapy. Clinical examination revealed best-corrected visual acuities of 20/80 OU, rare anterior chamber cell, 2+ vitreous cell, diffuse intraretinal hemorrhages, and exudative retinal detachments (RD). Optical coherence tomography of the macula showed central subretinal fluid with cystic intraretinal fluid OU. The findings were consistent with panuveitis and exudative RD in the setting of MM. He reported symptomatic improvement after plasmapheresis and oral prednisone initiation. CONCLUSION: Extensive, bilateral exudative RD and panuveitis are rare but potentially sight-threatening findings in patients with MM.

Delayed presentation of surgically induced scleral necrosis after I-BRITE procedure treated with immunosuppressive therapy.

Surgically induced scleral necrosis (SISN) is an uncommon complication of ocular procedures. Cosmetic eye-whitening surgery involves conjunctival and Tenon's capsule dissection, cautery, and mitomycin C application. We report the case of a 36-year-old white woman referred to our clinic for severe pain, scleral inflammation, and necrosis in both eyes 9 years after I-BRITE, an elective eye-whitening procedure. An extensive workup yielded negative results. The patient improved with aggressive lubrication and topical and high-dose systemic prednisone (60 mg), with recurrence upon steroid tapering. Concomitant weekly methotrexate was added, resulting in inflammatory control and allowing discontinuance of topical and oral steroids.

Ocular Surface Inflammatory Disorders (OSID): A Collective of Systemic Etiologies Which Cause or Amplify Dry Eye Syndrome.

The ocular surface inflammatory disorders (OSID) are caused by systemic disorders that conduct a persistent inflammatory reaction in the ocular adnexal connective tissues, such as the conjunctiva, lacrimal gland (LG) and meibomian glands (MGs), which cause an inflammatory dry eye. The etiologies of OSID are a subset of systemic pathologies such as graft versus host disease, Sjögren's syndrome, allergies, cicatrizing conjunctivitis, and more. These cause a purely inflammatory dry eye syndrome as a consequence of the persistent surrounding inflammation in the adnexal tissues, which is distinct from the age-related dry eye disease. A limitation toward management of these conditions is the lack of available biomarkers that can detect presence of inflammation and quantify damage on the conjunctiva and LG, even though these are considered to be drivers of the inflammatory milieu. The OSID and dry eye syndrome are caused by different immune cells which are not exclusively limited to T cell lymphocytes, but rather derive from an orchestrated multicellular immunologic response. Recognition of this syndrome is crucial to direct research in a direction that clarifies the potential role of inflammation and its associated immune phenotype on the conjunctiva and adnexal ocular tissues in OSID and dry eye syndrome. On this paper, we review the basic and clinical research evidence for the existence of OSID with focus on the different immune cells involved, the target tissues and potential consequences and OSIDs diagnostic and therapeutic implications.

Recurrent Multiple Evanescent White Dot Syndrome (MEWDS) Following First Dose and Booster of the mRNA-1273 COVID-19 Vaccine: Case Report and Review of Literature.

To report a rare case of a patient with two recurrent episodes of Multiple Evanescent White Dot Syndrome (MEWDS) associated with the second dose and second booster of the mRNA-1273 COVID-19 vaccine (Moderna), and to perform a literature review on COVID-19-vaccine-associated MEWDS. Case Report: A 31-year-old female was evaluated for a temporal scotoma and photopsias that started two weeks after the second dose of the Moderna COVID-19 vaccine. Dilated fundus findings were remarkable for unilateral, small whitish-yellow dots scattered around posterior pole of the left eye, consistent with a diagnosis of MEWDS. The symptoms resolved three months later without treatment. Approximately one year after the first vaccine, the patient received the second Moderna COVID-19 vaccine booster and experienced a recurrence of symptoms with an enlarged scotoma and similar examination findings. The patient was treated with a course of systemic corticosteroids with subsequent clinical improvement. Conclusion: Although uveitis following COVID-19 vaccines is rare, our case highlights a need for increased awareness amongst practitioners regarding COVID-19-vaccine-associated onset or recurrence of ocular inflammatory diseases.

Diagnosis and Management of Idiopathic Persistent Iritis after Cataract Surgery (IPICS).

PURPOSE: To investigate the diagnosis and management of patients with idiopathic persistent iritis after cataract surgery (IPICS). DESIGN: Retrospective interventional case series. METHODS: Patients diagnosed with IPICS were evaluated for demographic and clinical characteristics and immune blood markers. Those with more than 6 months of follow-up were evaluated for treatment efficacy to achieve remission (ie, absence of inflammation for 3 months), with either exclusive slow tapering of topical steroids or the need for systemic immunosuppression. RESULTS: Forty-five patients presented with IPICS. Most were African American (39, 86.7%) or female (33, 77.3%). Antinuclear antibodies were present in 23 (69.9%) of patients. Main complications were steroid dependency (38,84.4%), glaucoma (24,53.5%), and macular edema (11,37.5%). Thirty two patients presented treatment follow up. On these,the proposed treatment strategy achieved remission in 30 (93.8%) of cases in a mean of 6.1 months via tapering of topical steroids in 15 (46.9%) of patients. However, in 17 (53.1%) of cases, adjuvant anti-inflammatory systemic medication was indicated. Meloxicam use was associated with remission in 11 (64.7%) of these patients and, in a minority with persistent iritis, treatment was escalated to methotrexate, which was successful in 4 (100%) of the cases. CONCLUSIONS: IPICS is a distinct clinical anterior uveitis most common in African American and female patients, characterized by an unexpected onset of iritis after cataract surgery and high rates of steroid dependency, glaucoma, and macular edema. It is best treated with an initial slow taper of topical steroids; although adjuvant systemic anti-inflammatory therapy may be necessary to obtain remission and avoid complications.

A multicenter report of the use of plasma rich in growth factors (PRGF) for the treatment of patients with ocular surface diseases in North America.

PURPOSE: To investigate the efficacy and safety of plasma rich in growth factors (PRGF) eyedrops in the management of patients with ocular surface diseases in North America. METHODS: Multicenter interventional case series of patients using PRGF eyedrops for the first time. A cohort of patients was analyzed for corneal staining score at initial visit and at 3 months of therapy with PRGF. Another cohort responded to a 10-item questionnaire that evaluated patients' satisfaction and safety, which included the symptom assessment questionnaire in dry eye (SANDE) score, after 6 months of PRGF treatment. RESULTS: A total of 153 patients were analyzed. Of these, 102 were reviewed for corneal epitheliopathy and 99 patients responded to the questionnaire. The mean (±SD) age of the population was 63.7 ± 17 years and 72.5% were female. The clinical indications for PRGF usage were dry eye (60%), neurotrophic keratopathy (15%), dormant corneal ulcers (12%), limbal stem cell deficiency (10%), and cicatrizing conjunctivitis (4%). At the final visit, 74.3% of patients showed an improvement of their corneal staining. Those who had punctate epithelial erosions or epithelial defects were reduced from 76.5% to 47% and 23.5% to 7.8% respectively (p < 0.0001). Symptoms, measured via SANDE score, significantly decreased from a median of 90 to 34.6 out of 100 points on follow-up (p < 0.0001). Only one patient (0.98%) complained of ocular burning sensation as a side effect. CONCLUSIONS: This multicentric study demonstrates the safety and efficacy of the use of PRGF for treating signs and symptoms in patients with significant ocular surface diseases.

The evolution of the modified osteo-odonto-keratoprosthesis, its reliability, and long-term visual rehabilitation prognosis: An analytical review.

An exhaustive search of the world's literature was performed to analyze all case reports and series on the modified osteo-odonto-keratoprosthesis (MOOKP) published up to January 2022. The demographic profile, the primary indication for surgery, surgical technique variations, postoperative medical management, long-term functional and anatomical outcomes, and intra- and postoperative complications were analyzed and compared. Additionally, some of the authors' (GI, VP, and GA) unpublished MOOKP cases were studied. An extensive literature search yielded 37 case series and case reports. Overall, 958 patients were analyzed. The most common indication for surgery was autoimmune disease (39.1%), closely followed by chemical injury (38.8%). The most common intraoperative complications (21.67%) included maxillofacial, vitreous hemorrhage/vitritis, and mucosal. The most common postoperative complications (78.4%) were lamina and oral mucosa-associated, secondary glaucoma, and choroid/retinal detachment. Follow-up periods ranged from one to 364 months (median: 36.7 months). Altogether, 78% of patients achieved a visual acuity of 20/400 or better at the end of the follow-up period, and 91.2% improved at least temporarily after MOOKP surgery. Mean anatomic success at the end-of-follow-up for all patients was 88.25% (range, 50-100%). The long-term anatomic and functional success of the MOOKP makes it a reliable option for visual rehabilitation in patients with bilateral corneal blindness and end-stage ocular surface disease. This review aims to describe the evolution of the MOOKP procedure, analyzing all published case series for its long-term reliability, visual and anatomical outcomes, complications, and future directions.

Ophthalmological Approach for the Diagnosis of Dry Eye Disease in Patients with Sjögren's Syndrome.

Dry eye has two basic subdivisions: aqueous deficient dry eye (ADDE), with SS a major cause; and evaporative dry eye (EDE), due to either intrinsic or extrinsic factors. SS is a chronic inflammatory disorder defined by dysfunction of the exocrine glands leading to dry eye and dry mouth. The objective of this article was to carry out a systematic and critical review of several scientific publications on dry eye disease, with the aim of providing general recommendations to distinguish dry eye and its different variants in patients with SS, during the period 1979 to 2020, using search engines for articles indexed in Scopus, Latindex, Scielo, Clinical Trials, Medline, Embase, and Cochrane, allowing the analysis of 132 articles published in indexed journals on the subject of dry eye disease and SS, evidencing its conceptualization, prevalence, risk factors, etiopathogenesis, clinical manifestations, diagnosis, and treatment.

Multicenter prospective validation study for international chronic ocular graft-versus-host disease consensus diagnostic criteria.

PURPOSE: To validate the international chronic ocular graft-versus-host disease (GVHD) diagnostic criteria (ICCGVHD) compared to the National Institute of Health diagnostic criteria 2014 (NIH2014) for chronic ocular GVHD. METHODS: Between 2013 and 2019, the study enrolled 233 patients with or without chronic ocular GVHD combined with the presence or absence of systemic chronic GVHD in an internationally prospective multicenter and observational cohort from 9 institutions. All patients were evaluated for four clinical parameters of ICCGVHD. RESULTS: The relation between the ICCGVHD score (0-11) and NIH2014 eye score (0-4) was relatively high (r = 0.708, 95% CI: 0.637-0.767, p < 0.001). The sensitivity and specificity of ICCGVHD for NIH 2014 for 233 patients were 94.3% (95% CI: 89.6%-98.1%) and 71.7% (95% CI: 63.0-79.5%), respectively (cutoff value of the ICCGVHD score = 6). The positive predictive value was 77.1% (95% CI: 71.1%-82.1%), and the negative predictive value was 87.0% (95% CI:81.6-92.5%). For the patients with systemic GVHD (n = 171), the sensitivity and specificity were 94.2% and 67.2%, respectively (ICCGVHD-score cutoff value = 6). By receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.903 (95% CI: 0.859-0.948). For patients without systemic GVHD (n = 62), the sensitivity and specificity were 100% and 76.7%, respectively (ICCGVHD-score cutoff value = 6). The AUC was 0.891 (95% CI 0.673-1.000). CONCLUSIONS: Good sensitivity, specificity, predictive value and correlation were found between ICCGVHD and NIH2014. ICCGVHD scores ≥6 can be useful to diagnose ocular GVHD with or without systemic GVHD for clinical research.

Understanding Immune Responses to Surgical Transplant Procedures in Stevens Johnsons Syndrome Patients.

Stevens Johnsons syndrome (SJS) is a mucocutaneous disorder caused by an autoimmune response most commonly to medications. Unless it is properly managed in the acute setting, this entity can affect the ocular surface causing chronic cicatrizing conjunctivitis with limbal stem cell deficiency and lid anomalies which ultimately result in corneal opacities that may limit patients' visual acuity. When this stage is reached, some patients might need to undergo some form of corneal and/or limbal stem cell transplantation that exposes an already sensitized immune system to a new alloantigen. While the innate immunity plays a role in corneal graft survival, adaptive immune responses play a major part in corneal graft rejection and failure, namely through CD4+ T cell lymphocytes. Hence, the management of the immune response to surgical transplant procedures in SJS patients, involves a dual approach that modulates the inflammatory response to a new alloantigen in the context of an autoimmune sensitized patient. This review will explore and discuss current perspectives and future directions in the field of ocular immunology on how to manage SJS immune responses to ocular surgical procedures, reviewing systemic and local immunosuppressive therapies and protocols to adequately manage this debilitating condition.

Associated Neurotrophic Keratopathy in Complex Regional Pain Syndrome.

PURPOSE: To report a case of neurotrophic keratopathy (NK) in a patient with complex regional pain syndrome (CRPS) with ipsilateral facial involvement. METHODS: Case report. RESULTS: An 18-year old woman with a 5-year history of CRPS type I, a systemic disorder with a neuropathic component with associated limb and right facial involvement, presented with an insidious onset of blurred vision and pain in the right eye. Ocular examination revealed decreased corneal sensation, as measured by Cochet-Bonnet testing, associated with recurrent epithelial defects and whorl-like superficial corneal epitheliopathy. NK was suspected and confirmed by in vivo confocal microscopy (IVCM), which revealed rarefaction of the subbasal nerve plexus in the affected eye. To enhance corneal nerve health, plasma rich in growth factors drops were used. Persistence of NK prompted a superficial keratectomy with placement of an amniotic membrane graft and a course of cenegermin 0.002% (Oxervate; Dompé Farmaceutici SpA, Italy) in the postoperative period. This combination therapy resulted in successful epithelial closure and vision improvement after 8 weeks of therapy with no recurrence of disease for 11 months. Importantly, at that final visit, IVCM demonstrated growth of corneal nerves for the first time in this patient. CONCLUSIONS: This is the first case report of NK occurring in the context of CRPS, a neuropathy with ipsilateral facial pain involvement. IVCM was important in the diagnosis of NK, which responded successfully to ocular surface treatments focused on nerve health stimulation that ultimately resulted in corneal nerve growth.

Matrix metalloproteinase 9 positivity predicts long term decreased tear production.

PURPOSE: To investigate long-term correlations between Matrix Metalloproteinase-9 (MMP-9) testing and dry eye (DE) parameters. Additionally, to evaluate variability in MMP-9 results over time and with anti-inflammatory treatment. METHODS: Retrospective cohort study of DE patients with equal MMP-9 testing results (positive or negative) in both eyes and a minimum of 6 months of follow up. Our main outcome measure was to examine whether initial MMP-9 status affected change in DE parameters over time. Secondarily, we evaluated the frequency of MMP-9 status change over time and examined whether MMP-9 status change was impacted by treatment. RESULTS: 67 patients (76% female) fit the inclusion criteria. Mean age was 63 years with a mean follow up of 10.6 months. The majority (37/67, 55%) had concomitant systemic immune disease. MMP-9 testing was positive in both eyes in 39 individuals (58%) and negative in both eyes in 27 (42%) individuals. Of all DE parameters, initial MMP status predicted change in tear production. Individuals in the MMP-9 positive group had a greater decrease in production from baseline to final visit compared to the negative group (-2.6 vs 2.1, P = 0.013). In those initially MMP-9 positive, the frequency of becoming MMP-9 negative was higher in eyes treated with anti-inflammatory therapy compared to artificial tears (22.9% vs 3.3%, P = 0.106). However, only Lifitegrast 5% showed statistical significance compared to artificial tears (31.3% vs 3.3%, P = 0.044). CONCLUSIONS: Eyes with detectable MMP-9 had significantly decreased tear production over time compared to those without detectable MMP-9. Anti-inflammatory treatment more frequently normalized MMP-9 compared to PFATs.