Ocular surface changes in patients who have undergone head and neck radiation therapy.

PURPOSE: Dry eye syndrome (DES) is a familiar sequelae of radiation therapy (RT) for head and neck cancers (HNC). Ocular surface changes such as DES occur due to injury to the conjunctival epithelium, goblet cells, corneal surface, lacrimal glands, and meibomian glands. This study aimed at the evaluation and early detection of changes in ocular surface parameters in patients receiving RT for extraocular HNC. METHODS: Forty-two eyes of 21 patients undergoing HNC RT were evaluated. Radiation technique and dose of radiation to the lens and eye were recorded. Subjects were evaluated for meibomian gland changes by meiboscore grading, ocular surface disease index (OSDI) questionnaire, Schirmer's test, tear film break-up time (TBUT), and slit-lamp examination before RT, immediately post RT, and 6 weeks post RT. A comparison of the ipsilateral eye on the irradiated side to the contralateral eye was done. RESULTS: A significant reduction in TBUT was seen immediately post RT and 6 weeks post RT ( P < 0.001 and 0.008, respectively), with an increase in meiboscore at both visits ( P < 0.001). An OSDI score of >13 was seen in 23.80% of patients post RT, with a significant difference from baseline ( P < 0.001). On comparing ipsilateral and contralateral eye groups, a significant difference from baseline was seen in TBUT ( P < 0.001 and 0.033, respectively) and meiboscore ( P < 0.001 for both eyes). A significant change of >1 second in TBUT and >1.7 in meiboscore was seen with a mean dose of around 8 Gy to the lens. CONCLUSION: All patients undergoing HNC RT should be followed up for ocular surface and meibomian gland changes. The contralateral eye should also be evaluated. Patients receiving lower doses to the ocular structures should also be kept under follow-up.

Alterations in meibomian glands in patients treated with intensity-modulated radiotherapy for head and neck cancer.

Patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer may have increased incidence of dry eye disease and the exact mechanism is unclear. The present study aims to assess tear film and meibomian gland (MG) features in patients who received IMRT for head and neck cancer not involving the orbital area. Twenty-seven patients (64.7 ± 9.8 years) and 30 age-matched controls (61.4 ± 11.0 years) underwent a comprehensive dry eye work-up. Compared to the control group, the patients had more lid margin abnormalities, and worse meibum quality. The MG loss, calculated as (tarsal area-MG area)/tarsal area, was higher in the patient group in both the upper (53.0 ± 12.0% vs. 35.1 ± 10.3%, p < 0.001) and lower lids (69.5 ± 12.6% vs. 48.5 ± 12.5%, p < 0.001). In the patient group, more MG loss in the lower lids correlated with worse meibum quality (r = 0.445, p = 0.029). In contrast, there was no significant difference in aqueous tear production level, measured with Schirmer test. Patients treated with IMRT for head and neck cancer seemed to have comparable lacrimal gland function to the controls despite more dry eye symptoms. However, the patients had MG functional and morphological changes, which may present a higher risk for developing dry eye disease.

Effects of radiation therapy on the meibomian glands and dry eye in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Radiation therapy (RT) is the treatment of choice in patients with low-grade ocular adenexal mucosa-associated lymphoid tissue lymphoma (OAML) and many of them experience post-RT dry eye with varying severity. The purpose of the present study was to investigate ocular effects of RT on meibomian glands and dry eye by directly visualizing structural changes. Secondly, we focused on the comparison of two groups of patients according to tumor location and radiation technique. METHODS: Sixty-four eyes with OAML of conjunctiva, orbit, lacrimal gland, or lacrimal sac were grouped into conjunctival lymphoma and "orbital-type" lymphoma (i.e., orbit, lacrimal gland, and lacrimal sac). Subjects were investigated for morphological changes in meibomian glands by meiboscore grading system. Radiation technique was examined and Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test, tear film break-up time (TBUT), slit lamp examination of corneal surface and lid margin abnormality were conducted before and after RT. RESULTS: The increase in meiboscore was statistically significant over time after RT in both groups (P < 0.001). The extent of increase in meiboscore was significantly greater in the "orbital-type" lymphoma group than in the conjunctival lymphoma group (P < 0.001). The changes in OSDI, TBUT, corneal fluorescein staining score and lid margin abnormality score after RT were significantly different across two groups (P = 0.042, 0.001, 0.035 and 0.001, respectively). Schirmer's value decreased after RT in both groups. Dry eye symptoms were most severe right after RT in both groups, but a gradual resolution was noted in most patients with conjunctival lymphoma, whereas symptoms persisted in "orbital-type" lymphoma patients. The OSDI score and corneal fluorescein staining score were positively correlated with meiboscore in "orbital-type" patients at post-RT 6 months (r = 0.43, P = 0.04; r = 0.39, P = 0.03, respectively). CONCLUSIONS: Patients with OAML had different degrees of morphological changes in meibomian glands according to tumor location and radiation technique. "Orbital-type" lymphoma patients are more likely to experience severe injury to meibomian glands, which eventually leads to persistent dry eye. Patients with "orbital-type" lymphoma should be well informed of post-RT damage on meibomian glands and persistent dry eye.

Clinical results of Intraductal Meibomian gland probing combined with intense pulsed light in treating patients with refractory obstructive Meibomian gland dysfunction: a randomized controlled trial.

BACKGROUND: This study aims to optimize the therapeutic regimen for refractory obstructive meibomian gland dysfunction (o-MGD) patients by combining intraductal meibomian gland probing (MGP) and intense pulsed light (IPL) to enhance their positive effects and reduce their limitations. METHODS: This randomized, assessor blind study includes 45 patients (90 eyes) with refractory o-MGD who were divided into 3 groups via allocation concealment: IPL (group I, received an IPL treatment course: 3 times at 3-week intervals), MGP (group II, received MGP one time), and combined MGP-IPL (group III, MGP first followed by an IPL treatment course). Standard Patient Evaluation of Eye Dryness score (SPEED), tear break-up time (TBUT), corneal fluorescein staining (CFS), meibum grade, and lid margin finding results were assessed at baseline, 3 weeks after final treatment for groups I and III, 3 and 12 weeks after MGP for group II. Six months after final treatment, the SPEED and willingness to receive any treatment again were also collected for all groups. Paired Wilcoxon, Mann-Whitney U with Bonferroni correction, and Kruskal-Wallis tests were used for data analysis. RESULTS: For all 3 groups, all previously mentioned indexes improved significantly following treatment (P<0.01). MGP-IPL was better than IPL and MGP in terms of post-treatment SPEED, TBUT, meibum grade, and lid telangiectasia (P<0.05/3). Furthermore, the MGP-IPL was better than IPL in terms of lid tenderness and better than MGP in terms of orifice abnormality (P< 0.05/3). Six months later, the SPEED for the MGP-IPL was also significantly lower than other groups (P<0.05/3). Moreover, no patients in the MGP-IPL group expressed the need to be treated again compared to 35.7% or 20% of patients in the IPL or MGP groups, respectively. CONCLUSIONS: Compared with IPL or MGP alone, the combination MGP-IPL produced best results in relieving all signs and symptoms and helping patients attain long-lasting symptom relief. TRIAL REGISTRATION: http://clinicaltrials.gov , ChiCTR1900021273 (retrospectively registered February 9, 2019).

Intense Pulsed Light Therapy for Patients with Meibomian Gland Dysfunction and Ocular Demodex Infestation.

To observe the clinical changes of meibomian gland dysfunctipn (MGD) and ocular Demodex infestation after intense pulsed light (IPL) treatment to further examine the mechanism of IPL treating patients with MGD and ocular Demodex infestation. The medical records of 25 patients (49 eyes) with MGD treated with IPL, were retrospectively examined to determine outcomes. Associated ocular-surface parameters (ocular surface disease index, OSDI; lipid layer thickness, LLT; noninvasive first breakup time, NIF-BUT; noninvasive average breakup time, NIAvg-BUT; tear film breakup area, TBUA; Schirmer I Test, SIT; corneal fluorescein staining, CFS), eyelid margin abnormalities, meibum quality and expressibility, MG morphological parameters (macrostructure and microstructure), and the number of Demodex infestation were examined before and after treatment. The MG microstructure and the Demodex infestation were examined via in vivo confocal microscopy (IVCM). The results showed that there were statistically significant differences in associated ocular-surface parameters (all P<0.05) before and after IPL treatment, except SIT (P=0.065). Eyelid margin abnormalities, meibum quality and expressibility obviously improved in upper and lower eyelid after IPL treatment (all P<0.0001). MG macrostructure (MG dropouts) decreased in upper (P=0.002) and lower eyelid (P=0.001) after IPL treatment. The nine parameters of MG microstructure in upper and lower eyelid all distinctly improved after IPL treatment (all P<0.0001). The mean number of Demodex mites on the upper lid margin (6.59±7.16 to 3.12±3.81/9 eyelashes) and lower lid margin (2.55±2.11 to 1.29±1.53/9 eyelashes) significantly reduced after IPL treatment (all P<0.0001). The Demodex eradication rate was 20% (8/40) in upper lid margin and 34.15% (14/41) in lower lid margin. These findings indicate that IPL shows great therapeutic potential for patients of MGD and ocular Demodex infestation.

Further Investigations on the Crosslinking of Tarsal Collagen as a Treatment for Eyelid Laxity: Optimizing the Procedure in Animal Tissue.

PURPOSE: A follow-up experimental study on the exposure of animal tarsal plate to ultraviolet-A radiation aimed at establishing an optimum range for safe irradiation conditions. METHODS: Sheep tarsus specimens were excised postmortem and then subjected to irradiation with ultraviolet-A rays (wavelength 365 nm) at higher irradiances than those reported in an initial study, using a laboratory radiation source. The mechanical properties (tensile strength and Young's modulus) of irradiated and nonirradiated samples were evaluated in a mechanical tester. The test and control specimens were examined histologically with an aim to assess the effects of radiation upon the meibomian glands and tarsal collagen networks, and to establish a safe range for the exposure irradiance level. RESULTS: As expected, irradiation induced both stiffening and strengthening of the tarsal plate specimens. At an irradiance of 50 mW/cm for 3-minute exposure, these effects were at their maximum level, after which a decline in mechanical characteristics were observed. No destruction of the tarsal connective tissue or the meibomian glands were noticed up to an irradiance of 125 mW/cm for 3-minute exposure, corresponding to a fluence of 22.5 J/cm. Histology revealed that the collagen network surrounding the glands were packed more compactly following irradiation. At a fluence of 45 J/cm, massive destruction of periglandular collagen-rich network and meibocytes were demonstrated histologically. CONCLUSIONS: The study indicates that irradiation of tarsal collagen leading to tissue stiffening shall be carried out at levels of fluence between 10 and 15 J/cm, a region that is deemed safe. The exposure time can be adjusted according to the surgeon's decision.Safe irradiation conditions are established for the exposure of ex vivo ovine tarsus to ultraviolet-A radiation as a potentially effective treatment for eyelid laxity in human patients.

Long-term effects of intense pulsed light treatment on the ocular surface in patients with rosacea-associated meibomian gland dysfunction.

PURPOSE: We aimed to determine the long-term effects of intense pulsed light (IPL) treatment in rosacea-associated meibomian gland dysfunction (MGD). METHODS: We enrolled 17 rosacea subjects with moderate and severe MGD who underwent four IPL sessions at 3-week intervals and were followed up for 12 months. The subjects underwent clinical examinations at baseline (first IPL) and at 3 (second), 6 (third), 9 (fourth), and 12 weeks, as well as 6 and 12 months, after baseline. Ocular surface parameters, including the Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), staining score, and noninvasive Keratograph tear break-up time (NIKBUT), as well as meibomian gland parameters, including the lid margin vascularity and meibum expressibility and quality, were evaluated. RESULTS: All ocular surface and meibomian gland parameters for all subjects exhibited significant changes from baseline to the final examination (Friedman, P < 0.050 for all). In particular, improvements in the lower lid margin vascularity, meibum expressibility and quality, and ocular symptoms persisted up to the final examination (Wilcoxon, P < 0.050 for all). However, the improvements of TBUT, staining score, and NIKBUT after IPL were not maintained at 6 and 12 months after baseline. CONCLUSIONS: In rosacea-associated MGD, four IPL treatments at 3-week intervals can improve long-term lid parameters and ocular symptoms without adverse effects.

Intense Pulsed Light Applied Directly on Eyelids Combined with Meibomian Gland Expression to Treat Meibomian Gland Dysfunction.

OBJECTIVE: To determine the efficacy and safety of intense pulsed light (IPL) applied directly on the eyelids and meibomian gland expression (MGX) in treating meibomian gland dysfunction (MGD). BACKGROUND: IPL application on the periocular skin effectively improves meibomian gland secretion and tear film break-up time (TBUT) in patients with MGD/dry eye. METHODS: This prospective, randomized, double-masked, controlled study involved 44 patients. One eye was randomly selected for IPL treatment; the other served as a control. Study eyes received three IPL treatments at 4-week intervals; IPL was applied directly on the eyelids, and the eye was protected with a Jaeger lid plate. Control eyes received sham IPL treatments. Both eyes received MGX and artificial tears. Meibomian gland yielding secretion score (MGYSS), TBUT, Standard Patient Evaluation of Eye Dryness (SPEED), cornea fluorescein staining (CFS), meibography, best corrected visual acuity (BCVA), intraocular pressure (IOP), and fundus examination were performed. RESULTS: Compared to the baseline, MGYSS, TBUT, and SPEED and CFS scores improved in the study eyes, while only SPEED and CFS scores improved in the control eyes (p < 0.001 for all). Changes in MGYSS and TBUT were higher in the study eyes than in the control eyes (p < 0.05), but changes in SPEED and CFS scores were similar (p > 0.05). BCVA and IOP improved in both the study and control eyes (p < 0.05). Five patients experienced mild pain and burning during IPL treatment. One patient suffered partial eyelash loss. CONCLUSIONS: IPL combined with MGX safely and effectively treated MGD.

Changes in the Meibomian Gland After Exposure to Intense Pulsed Light in Meibomian Gland Dysfunction (MGD) Patients.

PURPOSE: To observe (1) changes in meibomian gland (MG) after exposure to intense pulsed light (IPL) and (2) to understand the mechanism by which IPL treats meibomian gland dysfunction (MGD) in patients. METHODS: A cohort study, including 35 MGD patients, was conducted. IPL treatment was administered in one group (IPL group; n = 18), and eyelid hygiene in another (control group; n = 17) for 3 months. All patients were given artificial tears during the treatment period. Associated ocular-surface indexes (ocular surface disease index, OSDI; tear breakup time, TBUT, Schirmer 1Test, corneal staining, and conjunctival staining), MG function, MG macro-morphology, and MG micro-morphology were examined before and after treatment. The relationships between the change in symptom score and the change in the other indexes (related ocular-surface indexes, MG functional indexes, and MG morphological indexes) were evaluated. RESULTS: There was no statistical difference in pretreatment between the IPL and the control groups in terms of age, gender, related medical history, MGD stage, and all examined indexes, with the exception of conjunctival staining. OSDI, TBUT, meibum quality, MG expressibility, and MG dropout improved after treatment in both of the two groups (all P < 0.05). The MG microstructure indexes, including the MG acinar longest diameter (ALD), MG acinar unit density (AUD), and the positive rate of inflammatory cells (ICs) around glandular structures were significantly improved in the IPL group. No improvements of microstructure were found in the control group. CONCLUSION: IPL treatment improves the symptom score of patients, associated ocular-surface indexes, MG function, and MG macrostructure as well as eyelid hygiene. And IPL treatment particularly improves MG microstructure and decreases MG inflammation in MGD patients.

Intense pulsed light treatment and meibomian gland expression for moderate to advanced meibomian gland dysfunction.

BACKGROUND: The aim was to evaluate the efficacy of periocular intense pulsed light therapy combined with meibomian gland expression for chronic dry eye due to moderate to advanced meibomian gland dysfunction. METHODS: This single-institution, open-label prospective study involved 26 participants who received bilateral treatments using a proprietary intense pulsed light device (E > Eye, E-Swin, Paris, France) combined with therapeutic meibomian gland expression at baseline, Week 2 and Week 6. Clinical evaluations performed at baseline, Week 4, Week 8 and Week 12 were symptom scores (Ocular Surface Disease Index [OSDI], Ocular Comfort Index [OCI], daily lubricant use, tear break-up time and ocular surface staining). Tear secretion, tear osmolarity, InflammaDry tear immunoassay, corneal sensation, meibomian secretion quality and expressibility, bulbar conjunctival, limbal and lid margin redness and eyelid margin bacterial swab for cultures and colony counts were performed at baseline and Week 8 only. RESULTS: Significant improvements occurred at Week 8 in meibomian gland expressibility (p = 0.002), meibum quality (p = 0.006), tear break-up time (p = 0.002), corneal staining (p = 0.001), lid margin redness (p = 0.001), bulbar redness (p = 0.05) and limbal redness (p = 0.001). Symptom survey outcomes, eyelid margin bacteria colony counts, Schirmer I test, tear osmolarity, corneal sensitivity and daily lubricant use were unchanged. At Week 12, significant improvements in symptoms (OSDI p = 0.025; OCI p = 0.003), tear break-up time (p = 0.001) and corneal staining (p = 0.001) occurred. Improvement in OSDI score was correlated to the improvement in ocular surface staining (R = 0.43, p = 0.03) and associated with baseline meibomian gland expressibility (Kendall tau: the distributions are ordered the same, p = 0.1). There were no adverse effects of treatment. CONCLUSIONS: Serial intense pulsed light therapy combined with meibomian gland expression significantly improved dry eye symptoms and clinical signs, including meibomian gland secretion quality and expressibility and ocular surface inflammation. Treatment effects were cumulative and sustained for at least six weeks after the final treatment.

Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis and ocular integrity in mice.

Sebocytes, which are characterized by lipid accumulation that leads to cell disruption, can be found in hair follicle-associated sebaceous glands (SGs) or in free SGs such as the Meibomian glands in the eyelids. Because genetic tools that allow targeting of sebocytes while maintaining intact epidermal lipids are lacking, the relevance of sebaceous lipids in health and disease remains poorly understood. Using Scd3, which is expressed exclusively in mature sebocytes, we established a mouse line with sebocyte-specific expression of Cre recombinase. Both RT-PCR analysis and crossing into Rosa26-lacZ reporter mice and Kras(G12D) mice confirmed Cre activity specifically in SGs, with no activity in other skin compartments. Importantly, loss of SCD3 function did not cause detectable phenotypical alterations, endorsing the usefulness of Scd3-Cre mice for further functional studies. Scd3-Cre-induced, diphtheria chain A toxin-mediated depletion of sebaceous lipids resulted in impaired water repulsion and thermoregulation, increased rates of UVB-induced epidermal apoptosis and caused a severe pathology of the ocular surface resembling Meibomian gland dysfunction. This novel mouse line will be useful for further investigating the roles of sebaceous lipids in skin and eye integrity.

Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction.

PURPOSE: To evaluate the effect of intense pulsed light (IPL) applied to the periocular area for meibomian gland dysfunction (MGD) in a prospective, double-masked, placebo-controlled, paired-eye study. METHODS: Twenty-eight participants underwent IPL treatment, with homogeneously sequenced light pulses delivered to one eye and placebo treatment to the partner control eye at 1, 15, and 45 days following baseline (BL) evaluation. Lipid layer grade (LLG), noninvasive tear break-up time (NIBUT), tear evaporation rate (TER), tear meniscus height (TMH), and subjective symptom score using visual analogue scales (VAS) were compared with BL and control values at each visit. RESULTS: Lipid layer grade improved significantly from BL to Day (D) 45 in the treated eye (P < 0.001), but not the control eye (P = 0.714), with 82% of treated eyes improving by at least one LLG. Noninvasive tear break-up time also improved significantly from BL to D45 in the treated (P < 0.001) but not in the control eye (P = 0.056) and was significantly longer than in the treated eye at D45 (14.1 ± 9.8 seconds versus 8.6 ± 8.2 seconds, P < 0.001). The tear evaporation rate was not different in the treated eye compared with the control eye at any visit. Tear meniscus height did not change from BL in either eye (P > 0.05). Visual analog scale symptom scores improved from BL in the treated (P = 0.015), but not the control eye (P = 0.245), with 86% of participants noting reduced symptoms in the treated eye by D45. CONCLUSIONS: Intense pulsed light with multiple sculpted pulses shows therapeutic potential for MGD, improving tear film quality and reducing symptoms of dry eye. ( https://www.anzctr.org.au number, ACTRN12614000162617.).