isotretinoin and Dry-Eye-Syndromes

To examine the effects of systemic isotretinoin treatment on the eye using several ocular examination parameters.. We conducted a systemic review for literature published up to June 2021 in both PubMed and Web of Science databases. We included prospective observational or interventional studies evaluating ocular manifestations of isotretinoin in acne patients. The primary outcome measures were anaesthetized and non-anaesthetized Schirmer test, tear break-up time (TBUT), central corneal thickness (CCT), average retinal nerve fibre layer (RNFL) thickness, ganglion cell-inner plexiform layer (GC-IP) thickness, subfoveal choroidal thickness, axial length, ocular surface disease index (OSDI), meibomian gland expression (MGE) and conjunctival stain. The National Institute of Health (NIH) quality assessment tools were used to assess the data quality. The effect size used to analyse the included studies was the weighted mean difference (WMD) and its related confidence intervals (95%CIs).. Twenty-one publications involving 1105 eyes of 842 participants met the inclusion criteria. Isotretinoin use was significantly associated with reduction in the scores of anaesthetized Schirmer (WMD = -2.23, 95%CI: -3.28 to -1.18), non-anaesthetized Schirmer (WMD = -3.74, 95%CI: -4.23 to -3.25), TBUT (WMD = -3.47, 95%CI: -5.09 to -1.86), and CCT (WMD= -7.39, 95%CI: -13.91 to -0.88). Isotretinoin use was significantly associated with increase of OSDI (WMD = 18.29, 95%CI: 7.54-29.03), MGE (WMD = 1.02, 95%CI: 0.70-1.33) and conjunctival stain scores (WMD = 0.61, 95%CI: 0.47-0.76). No significant change was noted in RNFL thickness (WMD = -0.64, 95%CI: -1.80 to 0.51); GC-IP thickness (WMD = 0.42, 95%CI: -1.08 to 1.92); subfoveal choroidal thickness (WMD = -1.80, 95%CI: -6.69 to 3.09), and axial length (WMD = 0.08, 95%CI: -0.19 to 0.35). A significant heterogeneity was found between the study estimates in each of anaesthetized Schirmer, TBUT, MGE, OSDI, and conjunctival stain tests.. Isotretinoin use results in a statistically significant reduction of the central corneal thickness, TBUT, and Schirmer test scores. A statistically significant increase in MGE, OSDI and conjunctival stain scores was found. No statistically significant change of average RNFL, GC-IP thickness, subfoveal choroidal thickness, or axial length was observed. Further well-designed studies should evaluate the long-term effect of isotretinoin on the eye and reach a firmer conclusion.

Topics: Acne Vulgaris; Dry Eye Syndromes; Humans; Isotretinoin; Meibomian Glands; Observational Studies as Topic; Tears

The authors have reviewed the potential etiology and long-standing consequences of isotretinoin use in the development of dry eye symptoms in the absence of significant clinical findings. Despite the normal appearance of meibomian gland structure on meibography and minimal signs of eyelid margin inflammation, the secretory function of these glands is reduced and symptoms of dryness can greatly impact a patient's quality of life. The available literature indicates that isotretinoin's effect on the meibomian glands likely mimics its effects on the sebaceous glands of the skin in the treatment of acne. Several representative cases seen at the University of California Berkeley School of Optometry Dry Eye Clinic provide a clinical paradigm with the goal of raising awareness of the potential prevalence of this disease in patients who experience symptoms of dry eye. These cases highlight the importance of meibomian gland expression in determining whether there is poor quality and/or quantity of meibum secondary to reduced gland function. Currently, there is no definitive method to restore the structure and function of damaged meibomian glands; thus, treatment options for isotretinoin-associated meibomian gland dysfunction are primarily palliative to manage patient symptoms.

Topics: Animals; Dermatologic Agents; Dry Eye Syndromes; Eyelid Diseases; Humans; Isotretinoin; Meibomian Glands; Tears

To investigate the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in patients receiving systemic isotretinoin therapy.. This is a prospective randomized study that included 180 eyes of 90 patients who had systemic isotretinoin therapy (120-150 mg/kg for at least 4-6 months). Exclusion criteria: DED according to the diagnostic criteria of TFOS DEWS II. Patients were assigned into three groups; (1) O3FAs/PPs group: A soft preloaded silicone plug was inserted in the inferior punctum of both eyes and received oral O3FAs two capsules twice daily total daily dose of 1040 mg/day for 6 months. (2) PPs group: A soft preloaded silicone plug was inserted in the inferior punctum of both eyes and received oral placebo. (3) Isotretinoin group: No intervention was done. At baseline, 1 week, 1, 3, and 6 months of study, Ocular surface evaluation tests were done in following order: OSDI, tear osmolarity, Schirmer's I test, TBUT, ocular surface staining score, and meibomian gland expression.. The changes in measurement of ocular surface evaluation tests including ocular surface disease index (OSDI), tear film breakup time (TFBUT), corneal staining, tear osmolarity, and meibomian gland expression at 6 months.. There are significant changes between all groups at 6 months follow-up. The ocular surface parameters were better for the PPs and O3FAs/PPs groups than the isotretinoin group. The isotretinoin group showed worsening of ocular surface parameters including a significant decrease of FTBUT and an increase of OSDI score, corneal staining score, tear osmolarity, and meibomian expression score. There was no significant difference in ST1 throughout the whole study in all groups. At 6 months follow-up, there were no statistically significant differences between PPs and O3FAs/PPs groups except meibomian expression score which showed a significant increase in PPs group.. Our cohort highlights the beneficial effects of the combination of O3FAs supplementation with PPs in the prevention of isotretinoin-associated OSD in this sample study.

Topics: Dry Eye Syndromes; Fatty Acids, Omega-3; Humans; Isotretinoin; Prospective Studies; Punctal Plugs; Tears

To investigate dry eye development in the patients receiving systemic retinoic acid therapy and to compare effectiveness of Autologous Serum (AS) and preservative free artificial tear (PFAT) in the patients with dry eye disease.. This prospective, crossover, double blind study was conducted on patients who have dry eyes due to systemic isotretinoin treatment for different indications. Patients detected as having dry eye during systemic isotretinoin treatment were included to our study. At baseline, 1 and 2 month of study, detailed ocular examination, best corrected visual acuity measurement, intraocular pressure measurement, and Tear Break-up Time (TBUT) and Schirmer Test (ST) without topical anesthesia were performed. We compared the efficacy of AS and PFAT. To accomplish crossover after the first month, treatment given to each patient was switched to the other treatment. Statistical analysis was measured using SPSS version 20.0. p values of < 0.05 were considered as statistically significant.. At the end of the first month, there was a significant improvement for the TBUT test in both AS and PFAT groups compared to baseline (respectively p < 0.001, p < 0.001). TBUT was found to be significantly higher in the AS group compared to the PFAT group at the end of the first month (p < 0.001). At the end of the second month, TBUT was found to be significantly higher in the AS group compared to the PFAT group at the posttreatment time (p < 0.001). There was a significant OSDI score decreasing in both groups compared to that reported previously at the end of the first and second months (respectively p < 0.001, p < 0.001). OSDI score decreasing was more significant in the AS group compared to the PFAT group at both time points (respectively p < 0.001, p < 0.001).. AS may be an effective alternative to PFAT in the treatment of dry eye developed during isotretinoin use.

Topics: Adult; Cross-Over Studies; Dermatologic Agents; Double-Blind Method; Dry Eye Syndromes; Female; Follow-Up Studies; Humans; Isotretinoin; Lubricant Eye Drops; Male; Ophthalmic Solutions; Prospective Studies; Serum; Skin Diseases; Tears; Time Factors; Treatment Outcome

To assess the ocular side effects during topical retinoid-antibiotic combination treatment in patients with facial acne vulgaris.. Forty-three patients applying topical isotretinoin+erythromycin combination (isotrexin gel, GlaxoSmithKline) once daily for the treatment of acne vulgaris were enrolled. Full ophthalmologic examination, Schirmer test (with topical anesthesia), fluorescein break-up time (BUT), corneal fluorescein staining and tear osmolarity measurement with the TearLab system (TearLab Corporation) were carried out before and at the end of the first month of the treatment. For evaluation of symptoms participants completed the ocular surface disease index (OSDI) questionnaire at each visit.. The mean age of the patients was 23.16±3.03 (18-30) years. Mean tear osmolarity increased significantly from 282.09±8.95 mOsm/L at baseline to 300.39±16.65 mOsm/L after the treatment (p<0.001). BUT decreased from an average of 11.93±1.12s at baseline to 6.65±3.03s at the end of the first month (p<0.001). The OSDI score worsened significantly (5.41±3.65 vs 21.53±12.95, p<0.001) and punctate epitheliopathy was seen in 51% of eyes after the treatment. The average Schirmer values were 13.09±1.90 and 12.41±2.44mm/5min before and at the end of the first month of the treatment, respectively (p=0.117).. The findings of this study indicate that topical retinoid-antibiotic combination treatment causes significant signs and symptoms of dry eye. Patients receiving topical treatment for acne should be evaluated regularly to ensure the timely detection and treatment of pathologic signs on the ocular surface.

Topics: Acne Vulgaris; Administration, Ophthalmic; Administration, Topical; Adolescent; Adult; Anti-Bacterial Agents; Dermatologic Agents; Drug Combinations; Dry Eye Syndromes; Erythromycin; Female; Humans; Isotretinoin; Male; Treatment Outcome; Young Adult

Topics: Acne Vulgaris; Administration, Oral; Adolescent; Adult; Dry Eye Syndromes; Humans; Isotretinoin; Keratolytic Agents; Male; Prospective Studies

To evaluate the effects of lipid-containing Rohto Dry Aid eye drops and sodium hyaluronate eye drops on the ocular surface and in vivo confocal microscopy (IVCM) findings in patients using systemic isotretinoin.. This retrospective study included 71 patients using systemic isotretinoin for acne vulgaris. Ocular surface and tear functions were evaluated with the tear break-up time (TBUT), corneal fluorescein staining (CFS), and the ocular surface disease index questionnaire (OSDI). Meibography was used for the staging of Meibomian gland dysfunction (MGD) while IVCM was used for the analysis of corneal micro-structural changes. The data of 36 patients using Rohto Dry Aid (the Rohto group) and 35 patients using sodium hyaluronate (the SH group) were recorded. Pre-treatment, first month and third month data were analyzed.. Longer TBUT, lower OSDI score, and less CFS were observed in the first and third months after treatment in the Rohto group (. Rohto Dry Aid, with its support of the lipid layer, is an effective and safe treatment agent that can improve both ocular surface and IVCM findings in evaporative dry eye cases with MGD.

Topics: Dry Eye Syndromes; Humans; Hyaluronic Acid; Isotretinoin; Lipids; Meibomian Glands; Microscopy, Confocal; Ophthalmic Solutions; Retrospective Studies; Tears

The aim of this pilot study was to quantify the meibography changes in patients administered with oral isotretinoin.. This prospective pilot study included 30 eyes of 30 patients who received oral isotretinoin treatment due to acne. Each patient underwent a general ophthalmological examination. After fluorescence staining of the ocular surface, the tear film break-up time (TFBUT) test, meibography and Schirmer test were carried out and noted. All of these procedures were applied before the treatment and repeated at 1, 3, and 6 months after the treatment.. The percentage of upper meibomian gland (MG) loss at 3 and 6 months after the treatment was 22.2% (p = 0.001) and 23.6% (p = 0.001), respectively. The percentage of lower MG loss at 3 and 6 months after the treatment was 18.7% (p = 0.001) and 20.7% (p = 0.001), respectively. The corneal fluorescein staining score at 3 and 6 months after treatment was 0.57 (p = 0.001), and 0.47 (p = 0.012), respectively.. These findings show that oral isotretionin treatment may affect MG morphology. The study findings also suggest that isotretinoin may cause tear film instability with Meibomian gland dysfunction and may cause evaporative type of dryness.

Topics: Dry Eye Syndromes; Humans; Isotretinoin; Meibomian Glands; Pilot Projects; Prospective Studies; Tears

To assess the effects of systemic isotretinoin therapy (SIT) on the ocular surface, meibomian glands (MG) and cornea microstructure in acne vulgaris (AV) patients.. Patients with AV (. This prospective study showed that systemic Isotretinoin treatment effects not only ocular surface parameters but also corneal and Meibomian glands structure. Considering early alterations in the course of treatment, ophthalmological assessment and follow-up during SIT are mandatory.

Topics: Acne Vulgaris; Dry Eye Syndromes; Fluoresceins; Humans; Isotretinoin; Longitudinal Studies; Meibomian Glands; Prospective Studies; Tears

The aim of study was to evaluate the effects of oral isotretinoin on meibomian gland (MG) morphology detected with non-contact meibography and to investigate its relation with clinical dry eye tests.. Forty-five acne patients treated with isotretinoin underwent a full ophthalmological examination at baseline and in the fourth month as follows: ocular surface disease index (OSDI) questionnaire, assessments of tear film break-up time (TFBUT), corneal fluorescein staining, Schirmer test, meibum expression, and lid margin abnormalities. Non-contact meibography imaging and noninvasive tear break up time (NI-BUT) assessments were also performed. The changes in MGs were scored (meibography score) as grade 0, no change; grade 1, mild; grade 2, moderate; and grade 3, marked.. There was a statistically significant change in OSDI, corneal fluorescein staining, lid margin abnormality, and meibum expression score during the treatment compared to baseline values (. The morphologic analysis using non-contact meibography is a useful method for assessing isotretinoin-related changes in MGs.

Topics: Dry Eye Syndromes; Eyelid Diseases; Humans; Isotretinoin; Meibomian Glands; Tears

To evaluate the changes in ocular surface and functions of tear-film in patients treated with systemic isotretinoin, to assess diagnostic performance of ocular surface disease index (OSDI) test in the dry eye conditions in association with the use of isotretinoin, and to determine the correlation between all tear-film function tests, OSDI and the dose and duration of isotretinoin administration. One hundred and twenty eyes of 60 subjects treated with oral isotretinoin were enrolled. All patients underwent ophthalmic examination at the baseline and another examination during the course of treatment. Biomicroscopic ophthalmic examination of the meibomian glands, non-anesthetized Schirmer test, and tear film break-up time (BUT) were performed. Subjective ocular complaints were scored with an OSDI questionnaire. Average Schirmer scores were not significantly changed by isotretinoin treatment. There were significant differences in the average OSDI score, the average meibomian gland disease (MGD) grade and average BUT value of both eyes during the treatment compared with baseline values (p < 0.01). There was a statistically significant inverse correlation between MGD grade and BUT value. There was no significant correlation between BUT value, OSDI score, Schirmer score, MGD grade, the total and divided dose of isotretinoin and the duration of treatment. The follow-up time was 4.01 ± 1.3 months (range 1.5-6 months). Systemic isotretinoin treatment can cause alterations in the tear film and dry eye symptoms. The OSDI test can be used as a diagnostic test for patients receiving systemic isotretinoin treatment.

Topics: Acne Vulgaris; Adolescent; Adult; Cornea; Dermatologic Agents; Dry Eye Syndromes; Eyelid Diseases; Female; Humans; Isotretinoin; Male; Meibomian Glands; Severity of Illness Index; Surveys and Questionnaires; Tears; Young Adult

Meibomian gland dysfunction (MGD) is a primary cause of dry eye disease. One of the risk factors for MGD is exposure to 13-cis retinoic acid (13-cis RA), a metabolite of vitamin A. However, the mechanism is not well understood. We hypothesize that 13-cis RA inhibits cell proliferation, promotes cell death, alters gene and protein expressions, and attenuates cell survival pathways in human meibomian gland epithelial cells.. To test our hypotheses, immortalized human meibomian gland epithelial cells were cultured with or without 13-cis RA for varying doses and time. Cell proliferation, cell death, gene expression, and proteins involved in proliferation/survival and inflammation were evaluated.. We found that 13-cis RA inhibited cell proliferation, induced cell death, and significantly altered the expression of 6726 genes, including those involved in cell proliferation, cell death, differentiation, keratinization, and inflammation, in human meibomian gland epithelial cells. Further, 13-cis RA also reduced the phosphorylation of Akt and increased the generation of interleukin-1β and matrix metallopeptidase 9.. Exposure to 13-cis RA inhibits cell proliferation, increases cell death, alters gene expression, changes signaling pathways, and promotes inflammatory mediator and protease expression in meibomian gland epithelial cells. These effects may be responsible, at least in part, for the 13-cis RA-related induction of MGD.

Topics: Cell Death; Cell Line, Transformed; Cell Proliferation; Cell Survival; Dermatologic Agents; Dose-Response Relationship, Drug; Dry Eye Syndromes; Epithelial Cells; Gene Expression; Humans; In Situ Nick-End Labeling; Interleukin-1beta; Isotretinoin; Matrix Metalloproteinase 9; Meibomian Glands; Proto-Oncogene Proteins c-akt; Signal Transduction

Topics: Acne Vulgaris; Contraindications; Dry Eye Syndromes; Humans; Isotretinoin; Keratomileusis, Laser In Situ; Postoperative Care; Preoperative Care

Isotretinoin (13-cis-retinoic acid) is commonly used for the treatment of acne vulgaris. In the skin this substance causes an atrophy of sebaceous gland acini and a decrease in sebum production. Systemic treatment also alters meibomian gland function and structure. These alterations seem to be responsible for ocular complications (dryness of the eye, blepharitis, conjunctivitis) during therapy with isotretinoin. We inspected 30 patients before, during and after therapy with isotretinoin with regard to ocular side effects. Examination included careful slit-lamp inspection, measurement of break-up time (BUT) and the Schirmer test. Conjunctival smears were taken from every patient. The most frequently observed side-effects were decreased tear break up time and alterations of the lid margin. In addition, an enormous increase of Staphylococcus aureus in conjunctival flora was noticed. However, all ocular complications of systemic treatment with isotretinoin were reversible after cessation of therapy.

Topics: Acne Vulgaris; Adolescent; Adult; Blepharitis; Conjunctiva; Conjunctivitis; Dry Eye Syndromes; Eyelids; Female; Humans; Isotretinoin; Male; Tears