Cutaneous Permeation of a Percutaneously Applied Glucocorticoid Using Plant-Based Anionic Phospholipids in Hydrogenated Vegetable Oil: A Preliminary Study.

Purpose: It is important that, when corticosteroids are used therapeutically, concentrations be reduced as much as possible to mitigate potential adverse events and side effects. This preliminary study compares the permeation for the delivery of a corticosteroid in a 1% hydrocortisone-supplemented topical cream containing anionic polar phospholipids (APP) in hydrogenated vegetable oil (triglyceride) versus a market-leading 1% hydrocortisone in a mineral hydrocarbon-based skin cream. Methods: Using the Franz diffusion cell method with cadaveric skin, the permeation of a 1% hydrocortisone-supplemented cream containing APP (test preparation) was compared with a commercially available 1% hydrocortisone cream (control preparation). The principal APP in the test preparation were phosphatidylinositol, phosphatidylserine and phosphatidylglycerol. Permeation was determined at 4 and 8 h time intervals. Results: The permeation values for the 1% hydrocortisone supplemental APP cream (test preparation) were comparatively very high 1180 ng/cm2 at 4 h and 2173 ng/cm2 at 8 h, in contrast to the 1% hydrocortisone cream (control preparation) values of 13 ng/cm2 at 4 h and 98 ng/cm2 at 8 h. Permeation of skin cream increased significantly from 0 to 4 and 8 h, when comparing the APP test preparation with the control preparation (p < 0.001). This translates, respectively, into the 90-fold greater and a 20-fold greater penetration of the test preparation APP cream over the 1% hydrocortisone cream at 4 h and 8 h time points. Conclusions: This preliminary study demonstrates the enhanced permeation of 1% hydrocortisone when applied topically to the skin in an APP skin cream vehicle. This enhanced permeation suggests the potential use of APP technology to deliver therapeutically effective hydrocortisone treatment to the skin at markedly reduced concentrations of steroid. As such, APP technology may offer an improved approach to the treatment of dermatoses associated with inflammatory diseases and conditions requiring prolonged topical corticosteroid therapy.

Corneal absorption of glycerylphosphorylcholine.

This study documents the absorption of glycerylphosphorylcholine (GPC) into corneas ex vivo. Corneas in quadruplicate were incubated in preservation medium containing 30 mM GPC, which is used as a reference marker. The GPC reference marker is used to calibrate 31P nuclear magnetic resonance (NMR) spectral chemical-shift positions for identification of phosphatic metabolites and to calculate intracorneal pH in intact tissues ex vivo. Following baseline NMR ex vivo analysis, corneas were stored in eye bank chambers in preservation medium containing 30 mM GPC at 4 °C overnight for 8 h. After returning to room temperature, NMR analysis was repeated on the same corneas in fresh GPC-free preservation medium. NMR analysis also was performed on the 30 mM GPC preservation medium alone from the eye bank chambers for detection of the GPC signal. The elevated GPC signal unexpectedly persisted in corneas incubated at 4 °C overnight even though GPC was not present in the fresh GPC-free preservation medium. In fact, the concentration of GPC in the intact cornea was many times higher than that found in the cornea endogenously. The levels of phosphatic metabolites and the energy modulus, after subtracting the spectral contribution of the 30 mM exogenous GPC, as well as the intracorneal pH remained unchanged from pre-refrigeration analyses. Corneas also retained transparency through the time-course of this study irrespective of temperature or change in temperature. The GPC signal in the NMR analysis of the preservation medium from the eye bank chambers was nearly undetectable. GPC was unexpectedly absorbed into the corneal tissue without detectable metabolic or physical toxicity. The intracorneal uptake of GPC at reduced temperatures parallels the increase in GPC that occurs naturally in muscle tissue in animals during wintering periods and the very high concentration of GPC in sperm, a cryogenically compatible cell, suggestive of a potential role for GPC in cryopreservation.

TFOS DEWS II Management and Therapy Report.

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

A Comparative Study Between an Oil-in-Water Emulsion and Nonlipid Eye Drops Used for Rewetting Contact Lenses.

OBJECTIVES: The purpose of this study was to determine the clinical impact of using SYSTANE BALANCE Lubricant Eye Drops (Alcon, Fort Worth, TX), an oil-in-water emulsion, as a rewetting eye drop in symptomatic contact lens wearers. METHODS: Subjects who had previously experienced contact lens discomfort (CLD), with a mean lens wearing history of 18.6±12.8 years, were randomly assigned to use a Test (SYSTANE BALANCE Lubricant Eye Drops; n=76) or control (habitual nonlipid contact lens rewetting eye drop; n=30) drop over their contact lenses within 5 min of lens insertion and then subsequently at 2 hr intervals up to a maximum of 4 drops per eye daily for a 1-month period. Assessments of subjective comfort, comfortable wearing time, lid wiper epitheliopathy (LWE), and corneal staining were conducted at baseline and after 1 month, after 6 hr of lens wear. RESULTS: Comfort, wearing time, LWE, and corneal staining all showed statistically significant improvements in the test group using SYSTANE BALANCE Lubricant Eye Drops at the 1-month visit compared with baseline data (all P<0.01) and compared with the control group at the 1-month visit (P<0.01, P=0.01, P<0.01, and P=0.03, respectively). CONCLUSIONS: The use of SYSTANE BALANCE Lubricant Eye Drops as a rewetting drop in a group of wearers who experienced symptoms of CLD improved subjective comfort scores, increased comfortable wearing time, and reduced signs of LWE and corneal staining, when compared with the use of non-lipid-containing contact lens rewetting eye drops.

All Warm Compresses Are Not Equally Efficacious.

PURPOSE: To investigate which warm compress (WC) methods used in a small case series are the most effective in providing heat to the inner eyelids for the supplemental treatment of meibomian gland dysfunction. METHODS: Inclusion criteria included the following: 18 years or older and willingness to participate in the study, no current ocular inflammation/disease, and no ocular surgery within the last 6 months. Five patients were fully consented and enrolled. Various forms of contact and noncontact WC heating methods (dry, wet/moist, and chemically activated dry heat) were tested. A paired contralateral design was used; each subject had a heated test eye and an unheated control eye. For both test and control eyes, the temperature of the external upper, external lower, and internal lower lids was measured at baseline and every 2 minutes for 10 minutes during application. Each participant underwent each of the eight treatments under study. Microwaved compresses were heated to 47 ± 1.0°C; two compresses were self-heating and thus not under investigator control. RESULTS: The mean (± SD) age of the patients was 42.2 (± 20.3) years. Out of the eight methods tested, the bundled wet/moist towel method was the only compress that elevated the temperature of all three lid surfaces (external upper, external lower, and internal lower lids) to 40°C or higher. The chemically activated EyeGiene, MGDRx EyeBag, and MediBeads compresses resulted in the lowest temperature increase at the inner palpebral surface. CONCLUSIONS: The Bundle method, although the most labor intensive, increased lid temperatures above therapeutic levels, as reported in the literature, for all measured sections during the WC application. As such, this method of WC application can be recommended for supplemental at-home therapy for meibomian gland dysfunction and any condition requiring that therapeutic heat of 40°C be administered to the meibomian glands.

Treatment for meibomian gland dysfunction and dry eye symptoms with a single-dose vectored thermal pulsation: a review.

PURPOSE OF REVIEW: Meibomian gland dysfunction (MGD) is understood to be a highly prevalent, chronic progressive disease and the leading cause of dry eye. All available published peer-reviewed results of the novel vectored thermal pulsation therapy for patients with MGD are investigated. RECENT FINDINGS: The PubMed and meeting abstract search revealed a total of 31 peer-reviewed reports on vectored thermal pulsation therapy at the time of the search (eight manuscripts and 23 meeting abstracts). All manuscripts evidence a significant increase in meibomian gland function (∼3×) and symptom improvement post a single 12-min treatment. Additional reported objective measures such as osmolarity, tear break-up time, or lipid layer thickness also increased as a result of the therapy; however, not all findings were statistically significant. The randomized controlled studies evidence sustained gland function and symptom relief lasting out to 12 months. The uncontrolled case series evidence significantly longer duration of effect. SUMMARY: A single 12 minute vectored thermal pulsation treatment allows for reducing dry eye symptoms, improving meibomian gland function and other correlates of the ocular surface health.

Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on meibomian gland functionality in patients with lipid deficient/evaporative dry eye.

PURPOSE: The aim of this study was to assess the efficacy of using a combination treatment approach consisting of lipid emulsion eye drops, eyelid cleansing wipes, and omega-3 vitamin supplements compared with warm compresses in improving meibomian gland functionality in patients with lipid-deficient/evaporative dry eye disease (LDDE). METHODS: This single-center, open-label, investigator-masked, randomized study enrolled patients aged ≥18 years, clinically diagnosed with LDDE defined as having ≤6 functional meibomian glands [meibomian gland yielding liquid secretion (MGYLS)] and positive for dry eye symptoms at screening. Patients were randomized to receive either the combination treatment (lipid emulsion eye drops, omega-3 supplements, and lid hygiene with eyelid wipes) or to apply warm, wet compresses once daily, 8 minutes per day, for 3 months. Meibomian gland functionality (number of MGYLS; primary outcome) and patient-reported subjective assessments (SPEED and OSDI questionnaires; secondary outcomes) were evaluated. Adverse events (AEs) and visual acuity were assessed as safety endpoints. RESULTS: Mean patient age was 41.7 years (n = 26; n = 13 per group). Mean ± SD number of MGYLS was not statistically significantly different between groups at baseline (combination treatment, 3.5 ± 1.5; warm compresses, 4.2 ± 1.4, P > 0.5), and was significantly greater with combination treatment versus warm compresses after 3 months of treatment (9.3 ± 2.7 vs. 4.7 ± 2.3; P = 0.006). Dry eye symptoms were significantly improved in both groups at all follow-up visits. Two AEs unrelated to treatment were reported; the BCVA was unchanged from baseline in both groups. CONCLUSIONS: The combination treatment regimen resulted in significant improvement in meibomian gland functionality and dry eye symptoms. No safety issues were observed.

Warm compresses and the risks of elevated corneal temperature with massage.

PURPOSES: To quantify the changes in corneal temperature resulting from intensive warm compress (WC) application with minimal pressure and to review the significance of these changes within the context of the peer-reviewed literature. METHODS: WC were applied intensively and unilaterally at 45 ± 0.5°C for 30 minutes with the contralateral eye serving as a control. Outer upper eyelid and central corneal surface temperatures were measured using an Infrared pyrometer at baseline. The WC were removed for repeat measurements of the outer upper eyelid surface and central corneal temperatures every 2 minutes and replaced with a new WC heated to 45 ± 0.5°C. Lid and corneal temperatures were monitored for 10 minutes after the final WC application. RESULTS: The mean age of the subjects was 37.1 ± 15.0 years (n = 12). The mean maximum outer upper lid temperature of 42.2 ± 1.3°C was reached after 6 minutes. The mean maximum corneal temperature of 39.4 ± 0.7°C was reached after 8 minutes of heating. The control eye showed no significant change in temperature from baseline throughout the experimental period. CONCLUSIONS: These data show that WC use for lid warming, even when only minimal contact pressure is applied, also transfers significant heat to the cornea. Corneal temperatures reach peak temperature after about 8 minutes of WC application. Recent reports discussing the increased potential for transient and long-term corneal molding subsequent to the heat and pressure of WC application are briefly reviewed.

Case report: a successful LipiFlow treatment of a single case of meibomian gland dysfunction and dropout.

OBJECTIVE: The aim of this study was to investigate whether a single case of meibomian gland dysfunction (MGD), with significant MG dropout resulting in evaporative dry eye, could be effectively treated with the LipiFlow (a new Food and Drug Administration-approved thermodynamic pulsatile treatment). MATERIALS AND METHODS: A 39-year-old white woman experienced severe dry eye symptoms because of MGD with considerable MG dropout resulting in evaporative dry eye. Standardized diagnostic MG expression and meibography led to the tentative diagnosis of nonobvious MGD (only 1 functional MG on each lower lid) and MG dropout (∼50% of the lower lid MGs were missing with the remaining MGs being severely truncated). The patient underwent a single 12-min LipiFlow treatment per eye and returned for follow-up at 1 and 7 months posttreatment. RESULTS: The LipiFlow treatment increased the number of functional lower lid MGs from 1 to 5 glands OD and 1 to 7 glands OS at 1 month with slight regression at 7 months (4 OD and 4 OS); increased fluorescein break-up time from 4 to 7 sec OD and 4 to 9 sec OS at both 1 and 7 months; and decreased symptom scores by approximately 50% at 1 month and approximately 75% at 7 months. CONCLUSIONS: These results demonstrate the effectiveness of the LipiFlow in restoring MG function and improving ocular comfort even in this particular case of significant MG dropout and MG truncation.

The role of heat in rubbing and massage-related corneal deformation.

PURPOSE: To examine the role of elevated corneal temperature in the development of rubbing/massage-related corneal deformation and the possibility that warm compresses in the management of meibomian gland dysfunction or chalazion could contribute to such adverse responses. METHODS: With reference to reports of corneal deformation associated with meibomian gland dysfunction, chalazion, dacryocystoceles and post-trabeculectomy, the mechanisms for increased corneal temperature due to ocular massage, especially when combined with warm compresses are examined. RESULTS: Several mechanisms for rubbing/massage to elevate corneal temperature have been described, apart from the application of warm compresses or other forms of heat. CONCLUSIONS: Raised corneal temperature helps to explain corneal deformation which develops in association with rubbing or massage in conditions such as keratoconus, chalazion, post-trabeculectomy, post-laser assisted in situ keratomileusis, post-graft and dacryocystoceles. When combined with warm compresses or other methods of heat delivery to the eye, the elevation of corneal temperature appears to explain how meibomian gland dysfunction treatment involving warm compresses and massage could induce rubbing-related deformation. Patients whose management involves iatrogenic ocular massage appear to require screening for risk of corneal deformation. Risk may be increased for patients with a concurrent habit of rubbing their eyes abnormally in response to allergic itch for example. It appears to be possible to modify ocular massage techniques to reduce the risk of corneal deformation. Careful tutoring and follow-up using corneal topography appears to be required when massage is prescribed, especially when used in conjunction with heat application.

A novel thermodynamic treatment for meibomian gland dysfunction.

PURPOSE: To evaluate a novel thermodynamic treatment for obstructive meibomian gland dysfunction (MGD). MATERIALS AND METHODS: Fourteen adult subjects (10 females, 4 males, mean age = 54.2 ± 9.6 yr) were recruited in a multi-center, feasibility clinical trial in Durham and Cary, North Carolina and Boston, Massachusetts. Inclusion criteria included: previous diagnosis of moderate to severe dry eye; dry eye symptoms for at least three months prior; daily topical lubricant use; and evidence of meibomian gland (MG) obstruction in the central five glands of both eyes lower eyelids. Exclusion criteria included: history of recent acute or chronic ocular inflammation or infection and lid surface abnormalities affecting lid function. The treatment: the device heats the palpebral surface of upper and lower eyelids while simultaneously applying graded pulsatile pressure to the outer eyelid for 12 min, thereby expressing the MGs during heating. One eye was randomly selected to undergo additional manual heated expression with another treatment device. RESULTS: The mean MG secretion score, tear break-up time, corneal staining score, number of MGs yielding liquid secretion and symptom scores all improved significantly from baseline to 1 week. This was maintained through the 3-month follow-up. There was no statistically significant difference in any outcome between the automated device treatment only and the additional heated manual expression. CONCLUSION: The combination of heat applied to the palpebral surface, while simultaneously expressing MGs during a single 12-minute treatment, was effective, in this feasibility study, in treating obstructive MG dysfunction and dry eye signs and symptoms for the 3-month study period.

Restoration of meibomian gland functionality with novel thermodynamic treatment device-a case report.

A new and previously unpublished thermodynamic treatment device, which for the first time applies heat directly to both inner eyelid surfaces with a precision-controlled resistive heater while pulsating pressure is simultaneously applied to the outer eyelids using an inflatable air bladder, was used to restore meibomian gland functionality for a subject with severe evaporative dry eye. The subject, a 39-year-old white woman of light complexion with severe symptoms and corroborating objective signs of dry eye, had been unsuccessfully treated for 3 years by 7 practitioners. Using a new standardized meibomian gland expression device, a diagnosis of nonobvious meibomian gland dysfunction, where none of the approximately 24 meibomian glands of the right lower eyelid and 1 meibomian gland of the left lower eyelid were functional, was made. The patient underwent a single 12-minute treatment per eye with the treatment device. The treatment restored the functionality of 8 glands in each eye, doubled the fluorescein break-up time (FBUT) from 5 to 10 seconds, and decreased the symptom scores by approximately 80% for the entire follow-up period of 3 months.

Inner eyelid surface temperature as a function of warm compress methodology.

PURPOSE: To (1) determine an optimal method of warm compress (WC) application to maximize heating meibomian glands in minimal time, (2) determine the maximum inner eyelid temperature achievable during 30 min of routine WC application, (3) examine the cooling curve for 10 min after WCs have been discontinued. METHODS: Subjects were randomly assigned to one of three WC methodologies. Group A (GrA), (n = 10): 15 min WC application without reheating. GrB, (n = 10): 30 min WC application with reheating every 2 min. GrC, (n = 12): 30 min WC application optimizing contact with the lower lid and reheating every 2 min. WCs were heated to 45 +/- 0.5 degrees C. Outer and inner lower eyelid surface temperatures were measured at baseline and regular intervals. RESULTS: GrA: the maximum outer and inner lower eyelid surface temperatures = 41.2 +/- 0.3 degrees C at 1 min and 38.8 +/- 0.2 degrees C after 4 min, respectively. GrB: the maximum outer upper eyelid temperature, 43.3 +/- 0.5 degrees C, was reached after 6 min while it required 30 min to reach the maximum inner lower eyelid temperature, 40.4 +/- 0.3 degrees C. GrC: it required 4 min to reach the maximum outer lower eyelid temperature, 42.2 +/- 0.4 degrees C, while it required 20 min to reach the maximum inner lower eyelid temperature, 40.8 +/- 0.3 degrees C. CONCLUSIONS: To optimize WC efficiency, patients should (1) heat the WC to approximately 45 degrees C, (2) optimize contact between the WC and outer eyelid surfaces, (3) reheat the WC frequently and have a replacement heated WC on hand for exchange, and (4) perform the activity for at least 4 min in order to achieve an inner lower eyelid temperature > or = 40 degrees C. Longer therapy may be necessary for more severe obstructions. These data suggest that precise, customized, labor-intensive WC procedure is necessary to optimize treating meibomian gland dysfunction and obstruction using WCs.

Warm compress induced visual degradation and Fischer-Schweitzer polygonal reflex.

PURPOSE: To document adverse visual effects of warm compress therapy and determine potential etiologies in subjects with dry eye symptoms. METHODS: Subjects (n = 24) with dry eye symptoms were recruited. Group 1 (n = 13): baseline measurements for each eye included subjective blur, visual acuity (VA), autorefraction (AR), corneal topography (CT), central corneal curvature (CCC), lipid layer thickness (LLT), and evaluation for corneal striae and edema. A warm, moist compress (44.4-45 degrees C) was applied with gentle pressure for 30 min to the closed eyelids of the randomized experimental eye; nothing was applied to the contralateral control eye. Subjective blur, VA, AR, CT, CCC, and LLT were evaluated for each eye at 5, 15, and 30 min and 5 min after application. Striae and edema were assessed for each eye at 30 and 5 min after application. Group 2 (n = 11): the above warm compress protocol was repeated to investigate the Fischer-Schweitzer polygonal reflex at the times stated. RESULTS: At 5 and 30 min, 71% and 88% of all subjects experienced increased subjective blur and decreased VA. At 30 min: Group 1: Of 13 experimental eyes: 13 experienced subjective blur; nine exhibited a VA decrease > or =2 lines (mean = 3.4 +/- 0.7). For the control eye, two subjects reported blur and none exhibited decreased VA. The findings for AR, CT, CCC, LLT, striae and edema did not correlate with blur or with VA decline. Group 2: Of 11 experimental eyes: 10 exhibited the polygonal reflex compared with 0 controls (p < 0.001); eight exhibited subjective blur; seven exhibited VA decrease > or =2 lines (mean = 2.9 +/- 0.9). The polygonal reflex correlated positively to visual blur (r = 0.88, p = 0.04) and to VA decrease (r = 0.79, p = 0.1). CONCLUSIONS: Warm compress application induces transient visual degradation. Although there was no correlation between visual degradation and AR, CT, CCC, LLT, or the presence of striae or corneal edema, visual degradation correlated positively with the polygonal reflex, which was observed following warm compress application.

Increase in tear film lipid layer thickness following treatment with warm compresses in patients with meibomian gland dysfunction.

PURPOSE: Warm-compress therapy applied to the skin of the closed eyelids has been recommended as a treatment for meibomian gland dysfunction (MGD). Previous studies have evaluated the effects of warm-compress therapy on tear-film fluorescein break-up time and tear evaporation rate. The purpose of this study was to determine if tear-film lipid layer thickness (TFLLT) was altered following 5, 15, and 30 minutes of warm, moist compress therapy. METHODS: Twenty patients with a diagnosis of dry eye associated with MGD and a baseline TFLLT of