Alternative therapies for dry eye disease.

PURPOSE OF REVIEW: Dry eye disease (DED) is a multifactorial disease affecting approximately 5-50% of individuals in various populations. Contributors to DED include, but are not limited to, lacrimal gland hypofunction, meibomian gland dysfunction (MGD), ocular surface inflammation, and corneal nerve dysfunction. Current DED treatments target some facets of the disease, such as ocular surface inflammation, but not all individuals experience adequate symptom relief. As such, this review focuses on alternative and adjunct approaches that are being explored to target underlying contributors to DED. RECENT FINDINGS: Neuromodulation, stem cell treatments, and oral royal jelly have all been studied in individuals with DED and lacrimal gland hypofunction, with promising results. In individuals with MGD, devices that provide eyelid warming or intense pulsed light therapy may reduce DED symptoms and signs, as may topical Manuka honey. For those with ocular surface inflammation, naturally derived anti-inflammatory agents may be helpful, with the compound trehalose being farthest along in the process of investigation. Nerve growth factor, blood-derived products, corneal neurotization, and to a lesser degree, fatty acids have been studied in individuals with DED and neurotrophic keratitis (i.e. corneal nerve hyposensitivity). Various adjuvant therapies have been investigated in individuals with DED with neuropathic pain (i.e. corneal nerve hypersensitivity) including nerve blocks, neurostimulation, botulinum toxin, and acupuncture, although study numbers and design are generally weaker than for the other DED sub-types. SUMMARY: Several alternatives and adjunct DED therapies are being investigated that target various aspects of disease. For many, more robust studies are required to assess their sustainability and applicability.

Barriers to the Effective Management of Gynecomastia in Adolescents.

BACKGROUND: The aim of this study was to explore the impacts of gynecomastia on adolescents, explore the surgical and psychological success of mastectomy, and evaluate the adequacy of insurance guidelines and coverage. METHODS: American College of Surgeons National Surgical Quality Improvement Program (NSQIP) surgical database from 2010 to 2014 was evaluated for current procedural terminology codes 19300 and 19303, representing mastectomies for gynecomastia and complete mastectomies respectively to compare surgical site complications. RESULTS: Of 1132 procedures for mastectomy for gynecomastia 1.5% of patients (n = 17) were associated with postoperative superficial surgical site complications. In the same timeframe, a total of 33,124 procedures for simple, complete mastectomy performed with a postoperative surgical complication rate of 2.2% (n = 721). Results of a Chi-squared goodness of fit χ (1, N = 34,997) = 2.10, P > 0.05 suggests no statistically significant difference between incidence of surgical site complications for a mastectomy for gynecomastia versus typical mastectomy. DISCUSSION: High surgical success rate, coupled with significant improvements in psychosocial functioning suggests that mastectomy is a highly effective intervention for adolescents with gynecomastia. However, due to vague and inadequate coverage and evaluation criteria surgery is often not performed. This paper offers a framework for developing a quantitative system by which to evaluate surgical candidates by adopting well-established guidelines currently in use for reduction mammoplasties and suggests further analysis into a cost/benefit analysis for coverage of the procedure.

The environment and dry eye-manifestations, mechanisms, and more.

Dry eye disease (DED) is a multifactorial condition that often presents with chronic symptoms of pain (that can be characterized as "dryness," "burning," and "irritation," to name a few) and/or fluctuating or poor-quality vision. Given its multifactorial nature, several pathophysiologic mechanisms have been identified that can underlie symptoms, including tear film, ocular surface, and/or corneal somatosensory nerve abnormalities. Research has focused on understanding how environmental exposures can increase the risk for DED flares and negatively impact the tear film, the ocular surface, and/or nerve health. Given that DED is a common condition that negatively impacts physical and mental functioning, managing DED requires multiple strategies. These can include both medical approaches and modulating adverse environmental conditions, the latter of which may be a cost-effective way to avoid DED flares. Thus, an understanding of how environmental exposures relate to disease is important. This Review summarizes research on the relationships between environmental exposures and DED, in the hope that this information will engage healthcare professionals and patients to consider environmental manipulations in their management of DED.

Outcomes of Secondary Intraocular Lens Implantation and Descemet Stripping Endothelial Keratoplasty-Comparing Staged Versus Combined Surgical Approach.

PURPOSE: The aim of this study was to compare the outcomes of staged versus combined surgical approach for secondary intraocular lens (IOL) implantation and Descemet stripping endothelial keratoplasty (DSEK). METHODS: This is a retrospective review of 124 eyes from 124 patients who underwent either staged or combined secondary IOL implantation in addition to DSEK over a 5-year period at 2 academic tertiary referral centers, between January 1, 2014, and October 1, 2019. Corrected distance visual acuity (CDVA), presence of graft detachment, primary graft failure (PGF), and cystoid macular edema were documented and analyzed. RESULTS: The CDVA for the 1- to 2- month follow-up period was significantly better in the staged group compared with the combined group ( P = 0.011). By the postoperative 6- to 9-month follow-up period, there was no significant difference in the CDVA between the groups ( P = 0.591). There was no significant difference in the incidence of PGF or graft detachment between the 2 groups ( P > 0.05). In addition, there was no significant difference in the CDVA or rate of postoperative complications between the different methods of IOL fixation. CONCLUSIONS: The short-term visual outcomes were significantly better in eyes that underwent staged secondary IOL implantation and DSEK versus the combined surgical approach, although the difference was no longer present at 6 to 9 months. There was no difference in the rate of PGF or graft detachment between the 2 groups.

Neuropathic ocular surface pain: Emerging drug targets and therapeutic implications.

INTRODUCTION: Dysfunction at various levels of the somatosensory system can lead to ocular surface pain with a neuropathic component. Compared to nociceptive pain (due to noxious stimuli at the ocular surface), neuropathic pain tends to be chronic and refractory to therapies, making it an important source of morbidity in the population. An understanding of the options available for neuropathic ocular surface pain, including new and emerging therapies, is thus an important topic. AREAS COVERED: This review will examine studies focusing on ocular surface pain, emphasizing those examining patients with a neuropathic component. Attention will be placed toward recent (after 2017) studies that have examined new and emerging therapies for neuropathic ocular surface pain. EXPERT OPINION: Several therapies have been studied thus far, and continued research is needed to identify which individuals would benefit from specific therapies. Gaps in our understanding exist, especially with availability of in-clinic diagnostics for neuropathic pain. A focus on improving diagnostic capabilities and researching gene-modulating therapies could help us to provide more specific mechanism-based therapies for patients. In the meantime, continuing to uncover new modalities and examining which are likely to work depending on pain phenotype remains an important short-term goal.

Corneal sub-basal nerve plexus microneuromas in individuals with and without dry eye.

BACKGROUND/AIM: An objective marker is needed to detect when corneal nerve abnormalities underlie neuropathic corneal pain (NCP), as symptoms often overlap with those of dry eye (DE). This study evaluated microneuroma (MN) frequency in various populations and investigated relationships between MN presence and DE clinical features in individuals with DE symptoms but without a history of refractive surgery, in order to eliminate refractive surgery as a potential confounder of nerve abnormalities. METHODS: This was a retrospective study that included individuals with and without DE symptoms who underwent a clinical evaluation for DE (symptom surveys and ocular surface evaluation) and in vivo confocal microscopy imaging. DE clinical features (including those suggestive of neuropathic pain) were compared based on MN presence using t-tests, χ2 analyses and Pearson's correlation coefficients with 0.05 alpha level. RESULTS: MN frequencies did not significantly differ between individuals with DE symptoms (Dry Eye Questionnaire 5 score ≥6) and a history of refractive surgery (n=1/16, 6%), individuals with DE symptoms without a history of refractive surgery (n=26/119, 22%) and individuals without DE symptoms (n=2/18, 11%, p=0.22). Among individuals with DE symptoms without a history of refractive surgery, DE clinical features, including those indicative of NCP (burning sensation and sensitivity to light, wind and extreme temperatures), did not significantly differ based on MN presence (p>0.05). CONCLUSION: MN frequencies did not significantly differ between individuals with and without DE symptoms. Their presence alone could not distinguish between DE subtypes, including features of NCP in our study population.

Differential Effects of Treatment Strategies in Individuals With Chronic Ocular Surface Pain With a Neuropathic Component.

Background: Dysfunction at the ocular system via nociceptive or neuropathic mechanisms can lead to chronic ocular pain. While many studies have reported on responses to treatment for nociceptive pain, fewer have focused on neuropathic ocular pain. This retrospective study assessed clinical responses to pain treatment modalities in individuals with neuropathic component ocular surface pain. Methods: 101 individuals seen at the University of Miami Oculofacial Pain Clinic from January 2015 to August 2021 with ≥3 months of clinically diagnosed neuropathic pain were included. Patients were subcategorized (postsurgical, post-traumatic, migraine-like, and laterality) and self-reported treatment outcomes were assessed (no change, mild, moderate, or marked improvement). One-way ANOVA (analysis of variance) was used to examine relationships between follow up time and number of treatments attempted with pain improvement, and multivariable logistic regression was used to assess which modalities led to pain improvement. Results: The mean age was 55 years, and most patients were female (64.4%) and non-Hispanic (68.3%). Migraine-like pain (40.6%) was most common, followed by postsurgical (26.7%), post-traumatic (16.8%) and unilateral pain (15.8%). The most common oral therapies were α2δ ligands (48.5%), the m common topical therapies were autologous serum tears (20.8%) and topical corticosteroids (19.8%), and the most common adjuvant was periocular nerve block (24.8%). Oral therapies reduced pain in post-traumatic (81.2%), migraine-like (73%), and unilateral (72.7%) patients, but only in a minority of postsurgical (38.5%) patients. Similarly, topicals improved pain in post-traumatic (66.7%), migraine-like (78.6%), and unilateral (70%) compared to postsurgical (43.7%) patients. Non-oral/topical adjuvants reduced pain in postsurgical (54.5%), post-traumatic (71.4%), and migraine-like patients (73.3%) only. Multivariable analyses indicated migraine-like pain improved with concomitant oral α2δ ligands and adjuvant therapies, while postsurgical pain improved with topical anti-inflammatories. Those with no improvement in pain had a shorter mean follow-up (266.25 ± 262.56 days) than those with mild (396.65 ± 283.44), moderate (652 ± 413.92), or marked improvement (837.93 ± 709.35) (p < 0.005). Identical patterns were noted for number of attempted medications. Conclusion: Patients with migraine-like pain frequently experienced pain improvement, while postsurgical patients had the lowest response rates. Patients with a longer follow-up and who tried more therapies experienced more significant relief, suggesting multiple trials were necessary for pain reduction.