ORIGINAL ARTICLE
Long-term effects of PAP on ocular surface in obstructive sleep apnea syndrome Mutlu Acar, MD,* Hikmet Fırat, MD,† Melike Yuceege, MD,† Sadik Ardıc, MD‡ ABSTRACT ● RÉSUMÉ Objective: To assess the long-term effects of positive airway pressure (PAP) therapy on the ocular surface and eyelid in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Design: Single-centred, prospective, and double-blinded study. Participants: Fifty-one patients with OSAHS. Methods: Fifty-one patients with OSAHS were treated with PAP for a period of 18 months. The pre- and post-PAP values for eye examination scores (presence of floppy eyelid syndrome [FES], results of the Ocular Surface Disease Index [OSDI] questionnaire, Schirmer I test, tear film break-up time [TBUT] values, and corneal staining stages) were compared. Results: Based on the apnea–hypopnea index, 17 patients were followed with moderate and 34 patients were followed with severe OSAHS. The presence of FES before and after PAP was 56.9% and 74.5% (p o 0.01). FES stage was determined as 1.41 ⫾ 0.98 before PAP and 0.78 ⫾ 0.78 after PAP (p o 0.01). Pre-PAP and post-PAP OSDI results were 47.79 ⫾ 21.04 and 42.17 ⫾ 19.97, respectively (p o 0.01). Schirmer values before and after PAP were 7.23 ⫾ 1.95 and 8.49 ⫾ 1.79 mm, respectively (p o 0.01). TBUT values before and after PAP were 7.11 ⫾ 1.82 and 8.68 ⫾ 1.76 seconds, respectively (p o 0.01). Scores of the corneal staining stages before and after PAP were 1.05 ⫾ 0.75 and 0.68 ⫾ 0.54, respectively (p o 0.01). Conclusions: OSAHS is associated with low Schirmer and TBUT values, and high scores in OSDI questionnaire, and high corneal staining stage. An appropriate PAP therapy helps to relieve both the systemic findings and the ocular surface problems most likely by providing a return to normal sleep patterns. We believe that long-term (at least 1 year) use of PAP improves the clinical picture of FES and can overcome the problem of ocular irritation that is encountered in the early stage of PAP. Objet : Évaluation des effets à long terme de la thérapie par ventilation à pression positive (VPP) sur la surface oculaire et les paupières de patients ayant un syndrome d'apnée ou d'hypopnée obstructive du sommeil (SAHOS). Nature : Étude prospective à centre unique et en double aveugle. Participants : 51 patients ayant un SAHOS. Méthode : Les 51 patients ayant un SAHOS ont été traités par VPP pendant 18 mois. L'on a comparé la valeur des résultats d'examen oculaire avant et après la VPP : présence d'un syndrome de paupière flottante (SPF), des résultats du questionnaire d'Indice de maladie de surface oculaire (IMSO), du test de Schirmer, du temps de rupture du film lacrymal (TRFL), et des étapes de coloration de la cornée. Résultats : Selon l'Indice Apnée-hypopnée, 17 patients ont été suivis pour un SAHOS modéré et 34 patients pour un SAHOS grave. La présence du SPF avant et après la VPP était 56,9 % et 74,5 % (po0,01). L'étape du SPF était déterminée à 1,41 ± 0,98 avant la VPP et à 0,78 ± 0,78 après la VPP (po0,01). Les résultats de l'IMSO avant et après la VPP étaient 47,79 ± 21,04 et 42,17 ± 19,97 (po0,01). Les valeurs Schirmer avant et après la VPP étaient 7,23 ± 1,95mm et 8,49 ± 1,79mm (po0,01). Les valeurs du TRFL avant et après la VPP étaient 7,11 ± 1,82 sec et 8,68 ± 1,76 sec. (po0,01). Les données des taches cornéennes avant et après la VPP étaient 1,05 ± 0,75 et 0,68 ± 0,54 (po0,001). Conclusions : Le SAHOS est associé à un Schirmer et un TRFL bas, ainsi qu'aux résultats élevés du questionnaire d'IMSO et au degré des taches cornéennes. Une thérapie appropriée par VPP aide à résoudre les problèmes systémiques ainsi que de la surface oculaire tout probablement en fournissant un retour aux habitudes de sommeil normal. Nous croyons qu'à long terme (au moins un an) l'utilisation du VPP améliore le bilan clinique du SPF et peut surmonter le problème d'irritation oculaire qui survient dans les premières étapes de la VPP.
The obstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by excessive daytime sleepiness, disruptive snoring, repeated episodes of upper airway obstruction during sleep, and nocturnal hypoxemia.1 The prevalence of OSAHS was observed to be 2% in women and 4% in men in the Wisconsin Sleep Cohort study.2 Sleep apnea has been shown to result in numerous medical complications and increased mortality if left
untreated.1 Overnight polysomnography (PSG) is the gold standard for the diagnosis of OSAHS.1,2 Positive airway pressure (PAP) remains the mainstay of treatment for moderate-to-severe obstructive sleep apnea in adults. PAP provides a “pneumatic splint” by delivering an intraluminal pressure that is positive with reference to the atmospheric pressure. The patient is hospitalized in another separate night for titration after the PSG. After a
From the *Ministry of Health, Department of Ophthalmology, Ankara Diskapi Yildirim Beyazit Training and Research Hospital; †Department of Chest Diseases and Sleep Center; ‡Acibadem Ankara Hospital, Ankara, Turkey
Correspondence to Mutlu Acar, MD, Ministry of Health, Ankara Diskapi Yildirim Beyazit Training and Research Hospital, Department of Ophthalmology, 06110, Ankara, Turkey; [email protected]
Presented as a poster presentation at the 46th Meeting of the Turkish Ophthalmology Society, Antalya, Turkey, Oct. 17–21, 2012.
Can J Ophthalmol 2014;49:217–221 0008-4182/14/$-see front matter & 2014 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2013.11.010
Originally received July 27, 2013. Final revision Nov. 16, 2013. Accepted Nov. 20, 2013 CAN J OPHTHALMOL — VOL. 49, NO. 2, APRIL 2014
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Effects of PAP in patients with OSA—Acar et al. patient is diagnosed with OSAHS, the current standard of practice involves performing full, attended PSG during which positive pressure is adjusted to determine optimal pressure for maintaining airway patency. This titration is used to find a fixed single pressure for subsequent nightly usage. PAP therapy has been demonstrated to be effective in reducing symptoms, cardiovascular morbidity and mortality, and neurocognitive sequel.3 Various eye disorders associated with OSAHS have been reported. These diseases include floppy eyelid syndrome (FES), cornea disorders, glaucoma, optic neuropathy, nonarteritic anterior ischemic optic neuropathy, and papilloedema.4–21 The ocular surface-specific findings observed in OSAHS include FES, papillary conjunctivitis, punctate epithelial keratopathy, recurrent corneal erosion, blepharochalasis, keratitis, and keratoconus.4–15 There are limited published studies on the effect of PAP therapy on the eye and ocular surface. These are in the form of either case reports or the effects of the short-term PAP treatment on the eye and ocular surface.22–29 We had demonstrated ocular diseases in patients with OSAHS in the first part of this study.4 In the second part of this study, PAP therapy was administered to the patients with moderate and severe forms of OSAHS for 18 months. The pre- and post-PAP eye examination findings were compared with respect to the presence of FES and FES stage, results of the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test results, tear film break-up time (TBUT) values, and corneal staining stages.
METHODS This is a single-centre and prospective study. The participants were evaluated for sleep pathologies by the same physician (H.F.). Patients presenting to the sleep centre with the complaints of snoring, witnessed apnea, and excessive daytime sleepiness underwent endoscopic examination by otorhinolaryngologist first. Those with anatomic nasal and chin deformities were excluded from the study. All the patients in the study underwent PSG (Compumedics, Melbourne, Victoria, Australia) during the whole night for 6 to 8 hours. The tecnique of the PSG is mentioned in detail in our previous report.4 Sleep stages and respiratory parameters were scored according to the standard criteria of the American Academy of Sleep Medicine (AASM). Based on the guidelines of the AASM published in 2007, apnea is defined as a Z90% decrease in airflow persisting for at least 10 seconds according to the basal amplitude. Hypopnea is defined as a Z50% decrease in the airflow amplitude relative to the baseline value with an associated Z3% oxygen desaturation or arousal, persisting for at least 10 seconds. Apnea–hypopnea index (AHI) was calculated based on the following formula: total number of obstructive apneas þ hypopneas / total sleep time (hours). Sleep
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stage scoring was done according to AASM criteria using software (Profusion PSG 3, Melbourne, Victoria, Australia) in 30-second epochs by a certified registered polysomnographic technologist.30 Two hundred eighty patients with OSAHS suspicion underwent PSG. Patients who agreed to participate in the study and those who had mean PAP usage duration Z4 hr/night were admitted to the second part of the study. PAP pressure for the treatment of airway obstruction was determined in accordance with the practice parameters of AASM.31,32 A total of 51 patients (17 moderate and 34 severe OSAHS) were included in the study. All 51 patients on PAP therapy with nasal mask were examined with their noninvasive mechanical ventilator devices, and the duration of usage was checked in each patient at the end of 18 months. Patients were excluded from the study if they had a history of using a diuretic, anti-inflammatory, antineoplastic, corticosteroid, immunosuppressive, antidepressant, or anxiolytic drugs within the last 2 months. Patients were also excluded if they had prior use of anticholinergic medications within 7 days of their ophthalmic examination. The ocular surface values were compared with the pretreatment values. The participants were evaluated for ocular symptoms by OSDI questionnaire by the same physician (M.Y.). A complete ophthalmologic examination involving visual acuity, intraocular pressure measurement, detailed anterior segment, and fundus examination was performed by the same physician (M.A.) blind to the OSAHS stages and OSDI questionnaire values of patients. Patients who were receiving drug treatment for ophthalmic diseases were also excluded from the study. We did not want to alter the clinical situation; thus, no patients were prescribed topical therapy for their FES or ocular irritation. Examination of eyelids and FES diagnosis
The diagnosis of FES was made based on the finding that the upper eyelid was easily everted on lifting the upper lid skin while the patient was looking down. The severity was graded as follows: 0 (no floppy eyelid), no tarsal conjunctiva visible; 1 (mild) ¼ less than one third of the upper tarsal conjunctiva visible; 2 (moderate) ¼ between one third and one half of the upper tarsal conjunctiva visible; and 3 (severe) ¼ more than half of the tarsal conjunctiva visible. OSDI questionnaire scoring algorithm
Questionnaires were completed before the examination to ensure that the clinical encounter would not influence the patients’ responses. The 12 items of the OSDI questionnaire were graded on a scale of 0 to 4, where 0 ¼ none of the time; 1 ¼ some of the time; 2 ¼ half of the time; 3 ¼ most of the time; and 4 ¼ all of the time. The total OSDI score was then calculated on the basis of the following formula: OSDI ¼ [(sum of scores for all
Effects of PAP in patients with OSA—Acar et al. questions answered) 100]/[(total number of questions answered) 4].33,34 Schirmer test
A standard Schirmer filter paper strip (Tear Flo Sterile Strips; Rose Stone Enterprises, Calif.) was inserted into the inferior lid margin 2 to 3 mm from the lateral canthus without using a topical anaesthetic agent. After 5 minutes, the moist part of the strip was measured starting from the edge of the eyelid; less than 6 mm of wetting after 5 minutes indicated a diagnosis of tear deficiency.35–37 TBUT
Fluorescein-soaked paper (Bio Glo Sterile Strips; Rose Stone Enterprises, Calif) was soaked in saline and put in contact with the lower fornix. After diffusion of the fluorescein, the tear film was examined using a blue cobalt filter. The time from the last blink to the appearance of the first dry spot was detected. The measurement was repeated 3 times and the mean value was calculated. The TBUT of less than 10 seconds suggests an unstable tear film.38,39 Corneal fluorescein staining
Cornea was evaluated using a blue cobalt filter after the TBUT measurement. Corneal staining was classified into 6 stages using the Oxford scheme.38,39 Informed consent was obtained from our patients, the ethics committee of our hospital approved the study, and the study was conducted in accordance with the tenets of the Declaration of Helsinki. We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research. Data were analyzed using the SPSS 10.0 software. One-way variance analysis was instituted for the Schirmer, TBUT, and OSDI data and the corneal staining; χ2 test was used for floppy eyelid data. Right and left eyes first analyzed separately, and if no difference was found between both results, only findings for the right eyes were analyzed in this study.
RESULTS A total of 51 patients, 19 female (37.2%) and 32 male patients (62.8%), was included in the study. The mean age was 48.12 ⫾ 10.54 (range 19–80) years. Based on the AHI, 17 patients (33.3%) had moderate OSAHS and 34
Table 1—Patient demographics AHI 15–30 430
OSAHS Grade
n
Sex (F/M)
Age, y
p
Moderate Severe
17 34
8/9 11/23
52.7 ⫾ 6.7 50.8 ⫾ 9.7
40.05 40.05
AHI, apnea–hypopnea index; OSAHS, obstructive sleep apnea hypopnea syndrome; F, female; M, male.
patients (66.7%) had severe OSAHS (Table 1). The patients were re-evaluated after 18 months of PAP treatment. FES was present in 74.5% before PAP and in 56.9% after PAP (p o 0.01). FES stage was determined as 1.41 ⫾ 0.98 before PAP and 0.78 ⫾ 0.78 after PAP (p o 0.01). OSDI scores were 47.79 ⫾ 21.04 before PAP and 42.17 ⫾ 19.97 after PAP (p o 0.01). Schirmer scores were 7.23 ⫾ 1.95 mm before PAP and 8.49 ⫾ 1.79 mm after PAP (p o 0.01). TBUT values were 7.11 ⫾ 1.82 seconds before PAP and 8.68 ⫾ 1.76 seconds after PAP (p o 0.01). Corneal fluorescein staining stage scores using the Oxford scheme were 1.05 ⫾ 0.75 before PAP and 0.68 ⫾ 0.54 after PAP (p o0.01).
DISCUSSION To the best of our knowledge, the largest series on OSAHS and eye findings have been reported in our previous study.4 Until now, there were a few case studies and 3 prospective studies that reported the effect of PAP treatment on the eye and ocular surface.22–29 Kiekens et al.24 reported that PAP treatment results in an increase in intraocular pressure. Harrison et al.25 encountered serious corneal and anterior segment complications in 3 cases with PAP therapy (keratoconus in 1 case, corneal degeneration in another case). Behbehani et al.26 detected ischemic optic neuropathy in 3 patients treated with PAP. Simaroj and Preechawat27 reported choroidal effusion in 1 patient after PAP therapy for 1 month. Ely and Khorfan28 reported unilateral periorbital edema in 1 patient after PAP therapy. Jain et al.29 reported a rapid regression of bilateral retinopathy in a patient with OSAHS with PAP therapy. FES was first described by Culbertson and Ostler5 in middle-aged, obese males. This syndrome is associated with easily everted floppy eyelids, papillary conjunctivitis, and recurrent corneal epithelial erosions.5–11 FES manifests with the symptoms of stinging, burning, itching, tearing, and redness. Patients reported that they had increased complaints upon waking up in the morning. Although the pathophysiology has not yet been clearly established, there are a number of suggested opinions. Based on 1 of these hypotheses, the mechanical compression resulting from friction, the position of lying, and tension cause ischemia in the eyelid and floppiness via tissue inflammation.8,11 Some studies reported low rates of association for OSAHS and FES with a prevalance rate of 4.5% to 5%.40,41 Mojon et al.6 reported an FES rate that was positively correlated with respiratory disturbance index values. We reported a positive correlation between the presence of FES and the OSAHS groups, and high rates and stages of FES in patients with severe OSAHS.4 In the CAN J OPHTHALMOL — VOL. 49, NO. 2, APRIL 2014
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Effects of PAP in patients with OSA—Acar et al. literature, only 1 study associated with FES and PAP. Kadyan et al.22 reported that there were no changes in eyelid laxity after treatment with PAP in patients with OSAHS. In our study, after 18 months of PAP therapy, we found a decline in the presence of FES and a regression in the FES stage compared with the baseline. With an appropriate, long-term PAP therapy for OSAHS, the sleep patterns of patients become normal, blood oxygen levels rise, and in particular eyelid ischemia diminishes. Because the patients receive this treatment in the supine position, the mechanical trauma of the eyelid is also reduced. We believe that the improvement of the clinical picture of FES after an appropriate, long-term PAP therapy is accomplished by the mechanisms described earlier. We reported the second Schirmer test results in the literature in OSAHS cases. We reported a negative correlation between the Schirmer values and the OSAHS groups. We also reported low levels of Schirmer I values in the severe disease groups based on AHI.4 In a study carried out with 40 patients with OSAHS, Hayirci et al.23 investigated the effect of 4 months of PAP therapy on the ocular surface. They found the pretreatment Schirmer values to be elevated near normal and elevated after the PAP therapy.23 This feature was explained by the irritative properties of PAP treatment. We also reported low levels of TBUT values in the severe disease groups based on AHI.4 Hayirci et al.23 found lower TBUT values after PAP compared with the baseline. This decrease in TBUT values was explained by the irritative properties of PAP treatment. Kadyan et al.22 reported increased TBUT values in patients with OSAHS after the application of PAP treatment with a more stable tear film. They have explained this improvement by the necessity of sleeping in the supine position during PAP therapy.22 In our study, we found an increase in the TBUT and Schirmer values after an appropriate, long-term PAP therapy, which was interpreted as healing of the ocular surface as a part of the improvement of the clinical situation of FES. The (Oxford) staging of the ocular surface by staining with vital dyes (fluorescein-lissamine green) was reported to have a significant role in the diagnosis, staging, and treatment follow-up of the diseases of the ocular surface.39 A correlation was reported between the grades of the staining of the ocular surface with vital stains and amount of tear production.42 We reported that the corneal staining stage scores showed an advanced type of staining pattern in the advanced groups by AHI.4 Hayirci et al.23 determined higher corneal staining scores after PAP treatment. They have explained the increased corneal staining scores by the irritative features of PAP therapy.23 In our study, we found a decline in the corneal staining scores after an appropriate, long-term PAP therapy, we believe it was associated with healing of tear function tests and increasing of ocular surface stability. The OSDI is a valid and reliable instrument for measuring the severity of ocular surface disease.33,34 We
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reported high levels of OSDI scores in the severe disease group based on AHI.4 Hayirci et al.23 found increased symptoms of ocular surface irritation after CPAP treatment. They reported increased symptoms of irritation due to the irritative features of CPAP therapy. Kadyan et al.22 described a decrease in ocular irritation in patients with OSAHS after the PAP therapy. They explained this with the necessity of the patient being in the supine position for PAP therapy and with the use of adequate respiratory equipment. In our study, we determined a decrease in the OSDI scores in patients with OSAHS, after an appropriate, long-term PAP therapy. We believe it was associated with healing of eyelid ischemia, FES, tear function tests, and improvement of ocular surface overall health. In conclusion, especially the moderate and severe forms of OSAHS are associated with low Schirmer and TBUT values, high OSDI results, high Oxford staining pattern stages, and the presence of FES. PAP is the most appropriate method in the treatment of OSAHS. An appropriate PAP therapy helps to relieve both the systemic findings and the ocular surface problems probably by reducing intermittent hypoxemias and arousals, and providing a better quality of sleep pattern. We believe that the long-term (at least 1 year) use of appropriate PAP therapy improves the clinical picture of FES and can overcome the problem of ocular surface irritation that is encountered in the early stage of PAP therapy. We believe, in these patients, the follow-up of the presence of FES and FES stage is the most effective method for monitoring the effectiveness of PAP therapy on the ocular surface. For a persistent improvement in the ocular surface in patients with OSAHS, we believe that PAP therapy should be implemented in an appropriate manner and under control. The patients who were examined for this study with OSAHS were using regular (at least 4 hr/day) CPAP therapy. Therefore, one of the weaknesses of this study is that the ophthalmologist was not blinded when performing the ocular examination.
Disclosure: The authors have no proprietary or commercial interest in any materials discussed in this article.
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Long-term effects of PAP on ocular surface in obstructive sleep apnea syndrome Mutlu Acar, MD,* Hikmet Fırat, MD,† Melike Yuceege, MD,† Sadik Ardıc, MD‡ ABSTRACT ● RÉSUMÉ Objective: To assess the long-term effects of positive airway pressure (PAP) therapy on the ocular surface and eyelid in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Design: Single-centred, prospective, and double-blinded study. Participants: Fifty-one patients with OSAHS. Methods: Fifty-one patients with OSAHS were treated with PAP for a period of 18 months. The pre- and post-PAP values for eye examination scores (presence of floppy eyelid syndrome [FES], results of the Ocular Surface Disease Index [OSDI] questionnaire, Schirmer I test, tear film break-up time [TBUT] values, and corneal staining stages) were compared. Results: Based on the apnea–hypopnea index, 17 patients were followed with moderate and 34 patients were followed with severe OSAHS. The presence of FES before and after PAP was 56.9% and 74.5% (p o 0.01). FES stage was determined as 1.41 ⫾ 0.98 before PAP and 0.78 ⫾ 0.78 after PAP (p o 0.01). Pre-PAP and post-PAP OSDI results were 47.79 ⫾ 21.04 and 42.17 ⫾ 19.97, respectively (p o 0.01). Schirmer values before and after PAP were 7.23 ⫾ 1.95 and 8.49 ⫾ 1.79 mm, respectively (p o 0.01). TBUT values before and after PAP were 7.11 ⫾ 1.82 and 8.68 ⫾ 1.76 seconds, respectively (p o 0.01). Scores of the corneal staining stages before and after PAP were 1.05 ⫾ 0.75 and 0.68 ⫾ 0.54, respectively (p o 0.01). Conclusions: OSAHS is associated with low Schirmer and TBUT values, and high scores in OSDI questionnaire, and high corneal staining stage. An appropriate PAP therapy helps to relieve both the systemic findings and the ocular surface problems most likely by providing a return to normal sleep patterns. We believe that long-term (at least 1 year) use of PAP improves the clinical picture of FES and can overcome the problem of ocular irritation that is encountered in the early stage of PAP. Objet : Évaluation des effets à long terme de la thérapie par ventilation à pression positive (VPP) sur la surface oculaire et les paupières de patients ayant un syndrome d'apnée ou d'hypopnée obstructive du sommeil (SAHOS). Nature : Étude prospective à centre unique et en double aveugle. Participants : 51 patients ayant un SAHOS. Méthode : Les 51 patients ayant un SAHOS ont été traités par VPP pendant 18 mois. L'on a comparé la valeur des résultats d'examen oculaire avant et après la VPP : présence d'un syndrome de paupière flottante (SPF), des résultats du questionnaire d'Indice de maladie de surface oculaire (IMSO), du test de Schirmer, du temps de rupture du film lacrymal (TRFL), et des étapes de coloration de la cornée. Résultats : Selon l'Indice Apnée-hypopnée, 17 patients ont été suivis pour un SAHOS modéré et 34 patients pour un SAHOS grave. La présence du SPF avant et après la VPP était 56,9 % et 74,5 % (po0,01). L'étape du SPF était déterminée à 1,41 ± 0,98 avant la VPP et à 0,78 ± 0,78 après la VPP (po0,01). Les résultats de l'IMSO avant et après la VPP étaient 47,79 ± 21,04 et 42,17 ± 19,97 (po0,01). Les valeurs Schirmer avant et après la VPP étaient 7,23 ± 1,95mm et 8,49 ± 1,79mm (po0,01). Les valeurs du TRFL avant et après la VPP étaient 7,11 ± 1,82 sec et 8,68 ± 1,76 sec. (po0,01). Les données des taches cornéennes avant et après la VPP étaient 1,05 ± 0,75 et 0,68 ± 0,54 (po0,001). Conclusions : Le SAHOS est associé à un Schirmer et un TRFL bas, ainsi qu'aux résultats élevés du questionnaire d'IMSO et au degré des taches cornéennes. Une thérapie appropriée par VPP aide à résoudre les problèmes systémiques ainsi que de la surface oculaire tout probablement en fournissant un retour aux habitudes de sommeil normal. Nous croyons qu'à long terme (au moins un an) l'utilisation du VPP améliore le bilan clinique du SPF et peut surmonter le problème d'irritation oculaire qui survient dans les premières étapes de la VPP.
The obstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by excessive daytime sleepiness, disruptive snoring, repeated episodes of upper airway obstruction during sleep, and nocturnal hypoxemia.1 The prevalence of OSAHS was observed to be 2% in women and 4% in men in the Wisconsin Sleep Cohort study.2 Sleep apnea has been shown to result in numerous medical complications and increased mortality if left
untreated.1 Overnight polysomnography (PSG) is the gold standard for the diagnosis of OSAHS.1,2 Positive airway pressure (PAP) remains the mainstay of treatment for moderate-to-severe obstructive sleep apnea in adults. PAP provides a “pneumatic splint” by delivering an intraluminal pressure that is positive with reference to the atmospheric pressure. The patient is hospitalized in another separate night for titration after the PSG. After a
From the *Ministry of Health, Department of Ophthalmology, Ankara Diskapi Yildirim Beyazit Training and Research Hospital; †Department of Chest Diseases and Sleep Center; ‡Acibadem Ankara Hospital, Ankara, Turkey
Correspondence to Mutlu Acar, MD, Ministry of Health, Ankara Diskapi Yildirim Beyazit Training and Research Hospital, Department of Ophthalmology, 06110, Ankara, Turkey; [email protected]
Presented as a poster presentation at the 46th Meeting of the Turkish Ophthalmology Society, Antalya, Turkey, Oct. 17–21, 2012.
Can J Ophthalmol 2014;49:217–221 0008-4182/14/$-see front matter & 2014 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2013.11.010
Originally received July 27, 2013. Final revision Nov. 16, 2013. Accepted Nov. 20, 2013 CAN J OPHTHALMOL — VOL. 49, NO. 2, APRIL 2014
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Effects of PAP in patients with OSA—Acar et al. patient is diagnosed with OSAHS, the current standard of practice involves performing full, attended PSG during which positive pressure is adjusted to determine optimal pressure for maintaining airway patency. This titration is used to find a fixed single pressure for subsequent nightly usage. PAP therapy has been demonstrated to be effective in reducing symptoms, cardiovascular morbidity and mortality, and neurocognitive sequel.3 Various eye disorders associated with OSAHS have been reported. These diseases include floppy eyelid syndrome (FES), cornea disorders, glaucoma, optic neuropathy, nonarteritic anterior ischemic optic neuropathy, and papilloedema.4–21 The ocular surface-specific findings observed in OSAHS include FES, papillary conjunctivitis, punctate epithelial keratopathy, recurrent corneal erosion, blepharochalasis, keratitis, and keratoconus.4–15 There are limited published studies on the effect of PAP therapy on the eye and ocular surface. These are in the form of either case reports or the effects of the short-term PAP treatment on the eye and ocular surface.22–29 We had demonstrated ocular diseases in patients with OSAHS in the first part of this study.4 In the second part of this study, PAP therapy was administered to the patients with moderate and severe forms of OSAHS for 18 months. The pre- and post-PAP eye examination findings were compared with respect to the presence of FES and FES stage, results of the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test results, tear film break-up time (TBUT) values, and corneal staining stages.
METHODS This is a single-centre and prospective study. The participants were evaluated for sleep pathologies by the same physician (H.F.). Patients presenting to the sleep centre with the complaints of snoring, witnessed apnea, and excessive daytime sleepiness underwent endoscopic examination by otorhinolaryngologist first. Those with anatomic nasal and chin deformities were excluded from the study. All the patients in the study underwent PSG (Compumedics, Melbourne, Victoria, Australia) during the whole night for 6 to 8 hours. The tecnique of the PSG is mentioned in detail in our previous report.4 Sleep stages and respiratory parameters were scored according to the standard criteria of the American Academy of Sleep Medicine (AASM). Based on the guidelines of the AASM published in 2007, apnea is defined as a Z90% decrease in airflow persisting for at least 10 seconds according to the basal amplitude. Hypopnea is defined as a Z50% decrease in the airflow amplitude relative to the baseline value with an associated Z3% oxygen desaturation or arousal, persisting for at least 10 seconds. Apnea–hypopnea index (AHI) was calculated based on the following formula: total number of obstructive apneas þ hypopneas / total sleep time (hours). Sleep
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stage scoring was done according to AASM criteria using software (Profusion PSG 3, Melbourne, Victoria, Australia) in 30-second epochs by a certified registered polysomnographic technologist.30 Two hundred eighty patients with OSAHS suspicion underwent PSG. Patients who agreed to participate in the study and those who had mean PAP usage duration Z4 hr/night were admitted to the second part of the study. PAP pressure for the treatment of airway obstruction was determined in accordance with the practice parameters of AASM.31,32 A total of 51 patients (17 moderate and 34 severe OSAHS) were included in the study. All 51 patients on PAP therapy with nasal mask were examined with their noninvasive mechanical ventilator devices, and the duration of usage was checked in each patient at the end of 18 months. Patients were excluded from the study if they had a history of using a diuretic, anti-inflammatory, antineoplastic, corticosteroid, immunosuppressive, antidepressant, or anxiolytic drugs within the last 2 months. Patients were also excluded if they had prior use of anticholinergic medications within 7 days of their ophthalmic examination. The ocular surface values were compared with the pretreatment values. The participants were evaluated for ocular symptoms by OSDI questionnaire by the same physician (M.Y.). A complete ophthalmologic examination involving visual acuity, intraocular pressure measurement, detailed anterior segment, and fundus examination was performed by the same physician (M.A.) blind to the OSAHS stages and OSDI questionnaire values of patients. Patients who were receiving drug treatment for ophthalmic diseases were also excluded from the study. We did not want to alter the clinical situation; thus, no patients were prescribed topical therapy for their FES or ocular irritation. Examination of eyelids and FES diagnosis
The diagnosis of FES was made based on the finding that the upper eyelid was easily everted on lifting the upper lid skin while the patient was looking down. The severity was graded as follows: 0 (no floppy eyelid), no tarsal conjunctiva visible; 1 (mild) ¼ less than one third of the upper tarsal conjunctiva visible; 2 (moderate) ¼ between one third and one half of the upper tarsal conjunctiva visible; and 3 (severe) ¼ more than half of the tarsal conjunctiva visible. OSDI questionnaire scoring algorithm
Questionnaires were completed before the examination to ensure that the clinical encounter would not influence the patients’ responses. The 12 items of the OSDI questionnaire were graded on a scale of 0 to 4, where 0 ¼ none of the time; 1 ¼ some of the time; 2 ¼ half of the time; 3 ¼ most of the time; and 4 ¼ all of the time. The total OSDI score was then calculated on the basis of the following formula: OSDI ¼ [(sum of scores for all
Effects of PAP in patients with OSA—Acar et al. questions answered) 100]/[(total number of questions answered) 4].33,34 Schirmer test
A standard Schirmer filter paper strip (Tear Flo Sterile Strips; Rose Stone Enterprises, Calif.) was inserted into the inferior lid margin 2 to 3 mm from the lateral canthus without using a topical anaesthetic agent. After 5 minutes, the moist part of the strip was measured starting from the edge of the eyelid; less than 6 mm of wetting after 5 minutes indicated a diagnosis of tear deficiency.35–37 TBUT
Fluorescein-soaked paper (Bio Glo Sterile Strips; Rose Stone Enterprises, Calif) was soaked in saline and put in contact with the lower fornix. After diffusion of the fluorescein, the tear film was examined using a blue cobalt filter. The time from the last blink to the appearance of the first dry spot was detected. The measurement was repeated 3 times and the mean value was calculated. The TBUT of less than 10 seconds suggests an unstable tear film.38,39 Corneal fluorescein staining
Cornea was evaluated using a blue cobalt filter after the TBUT measurement. Corneal staining was classified into 6 stages using the Oxford scheme.38,39 Informed consent was obtained from our patients, the ethics committee of our hospital approved the study, and the study was conducted in accordance with the tenets of the Declaration of Helsinki. We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research. Data were analyzed using the SPSS 10.0 software. One-way variance analysis was instituted for the Schirmer, TBUT, and OSDI data and the corneal staining; χ2 test was used for floppy eyelid data. Right and left eyes first analyzed separately, and if no difference was found between both results, only findings for the right eyes were analyzed in this study.
RESULTS A total of 51 patients, 19 female (37.2%) and 32 male patients (62.8%), was included in the study. The mean age was 48.12 ⫾ 10.54 (range 19–80) years. Based on the AHI, 17 patients (33.3%) had moderate OSAHS and 34
Table 1—Patient demographics AHI 15–30 430
OSAHS Grade
n
Sex (F/M)
Age, y
p
Moderate Severe
17 34
8/9 11/23
52.7 ⫾ 6.7 50.8 ⫾ 9.7
40.05 40.05
AHI, apnea–hypopnea index; OSAHS, obstructive sleep apnea hypopnea syndrome; F, female; M, male.
patients (66.7%) had severe OSAHS (Table 1). The patients were re-evaluated after 18 months of PAP treatment. FES was present in 74.5% before PAP and in 56.9% after PAP (p o 0.01). FES stage was determined as 1.41 ⫾ 0.98 before PAP and 0.78 ⫾ 0.78 after PAP (p o 0.01). OSDI scores were 47.79 ⫾ 21.04 before PAP and 42.17 ⫾ 19.97 after PAP (p o 0.01). Schirmer scores were 7.23 ⫾ 1.95 mm before PAP and 8.49 ⫾ 1.79 mm after PAP (p o 0.01). TBUT values were 7.11 ⫾ 1.82 seconds before PAP and 8.68 ⫾ 1.76 seconds after PAP (p o 0.01). Corneal fluorescein staining stage scores using the Oxford scheme were 1.05 ⫾ 0.75 before PAP and 0.68 ⫾ 0.54 after PAP (p o0.01).
DISCUSSION To the best of our knowledge, the largest series on OSAHS and eye findings have been reported in our previous study.4 Until now, there were a few case studies and 3 prospective studies that reported the effect of PAP treatment on the eye and ocular surface.22–29 Kiekens et al.24 reported that PAP treatment results in an increase in intraocular pressure. Harrison et al.25 encountered serious corneal and anterior segment complications in 3 cases with PAP therapy (keratoconus in 1 case, corneal degeneration in another case). Behbehani et al.26 detected ischemic optic neuropathy in 3 patients treated with PAP. Simaroj and Preechawat27 reported choroidal effusion in 1 patient after PAP therapy for 1 month. Ely and Khorfan28 reported unilateral periorbital edema in 1 patient after PAP therapy. Jain et al.29 reported a rapid regression of bilateral retinopathy in a patient with OSAHS with PAP therapy. FES was first described by Culbertson and Ostler5 in middle-aged, obese males. This syndrome is associated with easily everted floppy eyelids, papillary conjunctivitis, and recurrent corneal epithelial erosions.5–11 FES manifests with the symptoms of stinging, burning, itching, tearing, and redness. Patients reported that they had increased complaints upon waking up in the morning. Although the pathophysiology has not yet been clearly established, there are a number of suggested opinions. Based on 1 of these hypotheses, the mechanical compression resulting from friction, the position of lying, and tension cause ischemia in the eyelid and floppiness via tissue inflammation.8,11 Some studies reported low rates of association for OSAHS and FES with a prevalance rate of 4.5% to 5%.40,41 Mojon et al.6 reported an FES rate that was positively correlated with respiratory disturbance index values. We reported a positive correlation between the presence of FES and the OSAHS groups, and high rates and stages of FES in patients with severe OSAHS.4 In the CAN J OPHTHALMOL — VOL. 49, NO. 2, APRIL 2014
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Effects of PAP in patients with OSA—Acar et al. literature, only 1 study associated with FES and PAP. Kadyan et al.22 reported that there were no changes in eyelid laxity after treatment with PAP in patients with OSAHS. In our study, after 18 months of PAP therapy, we found a decline in the presence of FES and a regression in the FES stage compared with the baseline. With an appropriate, long-term PAP therapy for OSAHS, the sleep patterns of patients become normal, blood oxygen levels rise, and in particular eyelid ischemia diminishes. Because the patients receive this treatment in the supine position, the mechanical trauma of the eyelid is also reduced. We believe that the improvement of the clinical picture of FES after an appropriate, long-term PAP therapy is accomplished by the mechanisms described earlier. We reported the second Schirmer test results in the literature in OSAHS cases. We reported a negative correlation between the Schirmer values and the OSAHS groups. We also reported low levels of Schirmer I values in the severe disease groups based on AHI.4 In a study carried out with 40 patients with OSAHS, Hayirci et al.23 investigated the effect of 4 months of PAP therapy on the ocular surface. They found the pretreatment Schirmer values to be elevated near normal and elevated after the PAP therapy.23 This feature was explained by the irritative properties of PAP treatment. We also reported low levels of TBUT values in the severe disease groups based on AHI.4 Hayirci et al.23 found lower TBUT values after PAP compared with the baseline. This decrease in TBUT values was explained by the irritative properties of PAP treatment. Kadyan et al.22 reported increased TBUT values in patients with OSAHS after the application of PAP treatment with a more stable tear film. They have explained this improvement by the necessity of sleeping in the supine position during PAP therapy.22 In our study, we found an increase in the TBUT and Schirmer values after an appropriate, long-term PAP therapy, which was interpreted as healing of the ocular surface as a part of the improvement of the clinical situation of FES. The (Oxford) staging of the ocular surface by staining with vital dyes (fluorescein-lissamine green) was reported to have a significant role in the diagnosis, staging, and treatment follow-up of the diseases of the ocular surface.39 A correlation was reported between the grades of the staining of the ocular surface with vital stains and amount of tear production.42 We reported that the corneal staining stage scores showed an advanced type of staining pattern in the advanced groups by AHI.4 Hayirci et al.23 determined higher corneal staining scores after PAP treatment. They have explained the increased corneal staining scores by the irritative features of PAP therapy.23 In our study, we found a decline in the corneal staining scores after an appropriate, long-term PAP therapy, we believe it was associated with healing of tear function tests and increasing of ocular surface stability. The OSDI is a valid and reliable instrument for measuring the severity of ocular surface disease.33,34 We
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reported high levels of OSDI scores in the severe disease group based on AHI.4 Hayirci et al.23 found increased symptoms of ocular surface irritation after CPAP treatment. They reported increased symptoms of irritation due to the irritative features of CPAP therapy. Kadyan et al.22 described a decrease in ocular irritation in patients with OSAHS after the PAP therapy. They explained this with the necessity of the patient being in the supine position for PAP therapy and with the use of adequate respiratory equipment. In our study, we determined a decrease in the OSDI scores in patients with OSAHS, after an appropriate, long-term PAP therapy. We believe it was associated with healing of eyelid ischemia, FES, tear function tests, and improvement of ocular surface overall health. In conclusion, especially the moderate and severe forms of OSAHS are associated with low Schirmer and TBUT values, high OSDI results, high Oxford staining pattern stages, and the presence of FES. PAP is the most appropriate method in the treatment of OSAHS. An appropriate PAP therapy helps to relieve both the systemic findings and the ocular surface problems probably by reducing intermittent hypoxemias and arousals, and providing a better quality of sleep pattern. We believe that the long-term (at least 1 year) use of appropriate PAP therapy improves the clinical picture of FES and can overcome the problem of ocular surface irritation that is encountered in the early stage of PAP therapy. We believe, in these patients, the follow-up of the presence of FES and FES stage is the most effective method for monitoring the effectiveness of PAP therapy on the ocular surface. For a persistent improvement in the ocular surface in patients with OSAHS, we believe that PAP therapy should be implemented in an appropriate manner and under control. The patients who were examined for this study with OSAHS were using regular (at least 4 hr/day) CPAP therapy. Therefore, one of the weaknesses of this study is that the ophthalmologist was not blinded when performing the ocular examination.
Disclosure: The authors have no proprietary or commercial interest in any materials discussed in this article.
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