Technicians & Nurses Program

Transcription

1 ASCRS ASOA Symposium & Congress Technicians & Nurses Program April 17-21, 2015 San Diego, California

2 Charles S. Bouchard, MD, MA Course Title: Floppy Eyelids, Sleep Apnea and Keratoconus Saturday April 18, 2015 Session B: 2:15-3:15 SD CC Classroom 33ABC Lax Eyelids, Obstructive Sleep Apnea (OSA), and Ocular Disease Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS) 1. Overview a. Repetitive episodes of upper airway occlusion b. Loss of normal orpharyngeal tone-soft palate and base of tongue c. 30% reduction in airflow d. 3-4% oxygen desaturation and/or arousal e. Apnea/hypopnea index: (AHI) average number of episodes/hour f. Respiratory disturbance index (RDI): Number of arousals/hour 2. Epidemiology (USA) a. $115 Billion Total Annual Costs i. Less than: Cancer, Diabetes and Coronary Artery Disease ii. More than : Stroke, Hypertension, Asthma b. 25 Million Patients Affected c. 82% (19 Million) Undiagnosed d. 3. Symptoms a. Snoring b. Excessive daytime sleepiness or fatigue c. Witnessed apneas by bed partner d. Morning headaches e. Waking up choking or short of breath f. Insomnia 4. Physical Exam Features a. Floppy Eyelids b. Obesity c. Large neck circumference 1

3 d. Tonsillar hypertrophy e. Retrognathia 5. Pathophysiology a. Elastin Deficiency? (Present in lids of patients with floppy eyelid syndrome) b. Hypoxia from ischemia-reperfusion injury 6. Genetic Predisposition? a. + Family history of OSA with use of CPAP 7. Associated Systemic Diseases (Loyola study: 562,585 patients, 11,975 with OSA) a. Obesity (OR 20.2) b. Hypertension (OR, 9.4) c. Complications of organ transplant (GVHD?) (OR, 6.7) d. Diabetes Type 1 (OR, 5.2) e. Rosacea (OR, 3.8) 8. Associated Ocular Diseases a. Floppy (Lax) Eyelids (OR, 27) b. Chiasm disorders (OR, 9.2) c. Dry Eye Disease (OR 4.6) d. Glaucoma (OR, 4.5) e. Blepharitis (OR, 4.2) f. Rosacea Conjunctivitis (OR, 4.1) g. Papilledema (OR, 3.8) h. Keratoconus (OR, 3.6) i. Benign intracranial hypertension (OR, 3.3) 9. Management a. Continuous positive airway pressure (CPAP) Lax Eyelids (LEL), Lax Eyelid Syndrome (LES) and Floppy Eyelid Syndrome (FES) i. Overview a. Very common yet unrecognized disease b. Often managed (mismanaged) as dry eye disease c. Elevated ocular surface matrix metalloproteinases (MMPs) d. Strong association with obstructive sleep apnea (OSA) i. OSA associated with significant systemic and ocular morbidity e. Significant opportunity to benefit patients by recognizing FES and making referral for sleep study 2

4 ii. Definitions (Fowler AM et al, OPRS, 2010) a. Floppy eyelid syndrome (FES) (Culbertson et al, 1981, AJO) i. Rubbery, malleable, upper tarsus ii. Associated with papillary conjunctivitis iii. Obese males b. Lax Eyelid and Lax Eyelid Syndrome (LES) (Van den Bosch (1994, BJO) i. Distensible eyelids with Normal body mass index (BMI) ii. Relationship between LES and OSA not yet determined iii. Lower lid laxity atypical of the FES originally described iv. Lax eyelid as clinical feature rather than syndrome? v. Need to evaluate in all patients c. More severely affected eye: more severe symptoms i. Sleep preference side ii. Higher tear evaporation rate iii. Shorter tear break up time (TBUT) iv. Higher skin temperature, Higher skin evaporation rate d. Grading of upper eyelid laxity i. Horizontal distraction (Movement of lower punctum (mm)) ii. Proportion of upper tarsal conjunctiva exposed with traction (Liu et al 2005) iii. Strain gauge (Karger 2006) iv. Bouchard-Fowler Laxometer (Katena, Inc,) iii. Clinical Features a. Ocular Associations i. Eyelid 1. Easily everted upper eyelid 2. Skin hyperpigmentation 3. Dermatochalasis 4. Aponeurotic blepharoptosis 5. Eyelash Ptosis 6. Ectropion 7. Blepharitis, rosacea blephartiis 8. Demodex brevis 9. Meibomianitis ii. Cornea 1. Punctate keratopathy 2. Scarring 3

5 3. Neovascularization 4. Filamentary keratitis 5. Recurrent corner erosion 6. Ulcerative microbial keratitis, bilateral? 7. Thinning, perforation-rare 8. Keratoconus a. Often but not always same side of sleep preference b. Criteria of KCN unclear in several articles c. Association might be underestimated iii. Tear Film 1. Lipid tear film deficiency a. Kinetic tear interference imaging 2. Vertical lipid spread 3. Deficient lipid 4. Uneven spread 5. Punctate keratitis iv. Infrared thermometry 1. Higher ocular (and mouth) skin temperature v. Conjunctiva 1. Chronic papillary conjunctivitis a. Traumatic b. Nocturnal eversion Epithelial and stromal changes c. Non specific d. Chronic exposure? e. Non specific findings lead to delay in diagnosis 2. Other conjunctivitis a. Allergic b. Mechanical: Associated with rubbing? vi. Globe 1. Luxation of the Globe b. Systemic Associations (reported) i. Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) 1. OSAHS as causative factor a. Artifact of sample bias, questions about the etiology of disease 2. FES resolving with CPAP as therapy? 4

6 3. OSAHS associated with significant morbidity a. Cardiovascular b. Cerebral sequelae ii. Diabetes iii. Arterial Hypertension iv. Obesity v. Hyperlipidemia vi. Chronic Bronchitis vii. Psoriasis viii. Hyperglycemia ix. Paraparesis x. Schizophrenia xi. Pachydermoperiostitis xii. Eye rubbing xiii. Cocaine use xiv. Severe learning disabilities xv. Epibulbar nodular fasciitis xvi. Congenital cataracts xvii. Facial dysmorphism neuropathy iv. Treatment a. Medical i. Shield at bedtime ii. Lid taping iii. Nocturnal lubrication iv. Topical steroids v. Lid scrubbing vi. CPAP for OSAHS a. Therapeutic? (McNab 2000) b. Surgical i. Punctual plugs ii. Lid tightening procedures 1. Full thickness wedge excision (FTWE) i. Dutton Medial FTWE with blepharoplasty i. Valenzuela Lateral FTWE i. Periman

7 4. Large FTWE with vertical shortening of tarsal plate i. Madjilessi Lateral tarsorrhaphy i. Permanent or temporary Bouchard Lateral Tarsal Strip (LTS) i. Tensely 1977 first described ii. For FES Gerner 1984 Burkett 2005 iii. Bilateral upper lid, lower lid LTS with posterior advancement flaps 7. Lateral canthal tendon plication iii. Long term follow up/recurrence 1. Recurrence (Moorefield's) 2. 42% since 1995 v. Pathology a. Culbertson 1981 i. Conjunctival scrapings ii. Tarsoconjunctival biopsy 1. Non specific keratinization 2. Inflammatory papillary reaction iii. Tarsal extra cellular matrix (ECM) 1. Normal structures (TEM) 2. Stains normal i. Elastin and collagen b. Gonnering and Sonneland 1987 i. Meibomianitis ii. TEM: tarsal lipomatous atrophy iii. Demodex brevis iv. High incidence of Demodex folliculorum c. Netland et al 1994 i. Conjunctival inflammation (not in the tarsus) ii. Conjunctival keratinization iii. No glycosaminoglycans, amyloid, or proteoglycans abnormalities iv. Decrease quantity of elastin 1. Not uniform distribution 2. Thick elastin network around meibomian glands 6

8 vi. 3. Decrease in orbicularis endomysium 4. Controls not age matched in study d. Schlotzer-Schrehardt 2005 i. Conjunctival keratinization ii. Widened meibomian gland ducts iii. Subepithelial inflammation iv. Meibomian gland poor areas 1. Absence of elastin v. Meibomian gland rich areas 1. Elastin around gland acini vi. Eyelid skin 1. Reduction in elastin around ciliary roots 2.? explanation for lash ptosis vii. Matrix metalloproteinases (MMP) 1. MMP-2 in conjunctival epithelium (EP) e. FES as subset of Ehlers Danlos Syndrome (EDS) i. 6 subtypes (1997) ii. Collagen V mutation iii. Classic EDS iv. Functional Implications 1. Elastic tissue recoil, compliance 2. Fibrillation collagen 3. Tensile strength 4. Comparison with cutix laxa, loose and inelastic 5. Collagen disorders, EDS gives rise to elasticity Etiological Hypotheses a. Mechanical i. Symptoms common on side of sleeping preference ii. Symptoms of discomfort iii. Worse on awakening iv. Eye rubbing disorders v. Similar to KCN b. Poor Globe Apposition i. Not well supported ii. Sleeping side preference not 100% iii. Some tarsal degeneration leads to upper lid laxity c. Ischemia Reperfusion Injury i. Support by FES and OSAHS association 7

9 vii. ii. OSAHS associated with low nocturnal PaO 2 iii. Pressure induced ischemia on sleep preference side iv. Reperfusion 1. Release free radicals 2. Tarsal stromal damage 3. PMN migration 4. Conjunctivitis 5.? Ectatic changes Conclusions a. FES is a multisystem disease with protean manifestations and associations b. Eyelid laxity should be routinely examined c. FES on the differential diagnosis of patients with chronic conjunctivitis d. Patients with a diagnosis of FES would benefit from a referral for sleep study Obstructive Sleep Apnea and Glaucoma 1. Glaucoma a. Overview i. Progressive optic neuropathy with slow progressive degeneration of retinal ganglion cells and their axons ii. Most common cause of irreversible blindness in the world b. Classification i. Categorized into large groups- Primary and Secondary and Open angle vs Closed angle c. Characteristic findings i. Cupping of ONH ii. Visual field defect iii. Thinning of RNFL iv. Increased IOP is one of main contributing factors d. Pathophysiology i. Elevated IOP is thought to compromise retinal ganglion cell axons and lead to degeneration and cell death ii. Other processes may contribute to the death of retinal ganglion cells and optic nerve fibers iii. Dysfunctional blood flow autoregulation leading to ischemia and hypoxia oxidative stress with the formation of inflammatory cytokines and free radicals 2. OSA and glaucoma 8

10 a. Overview i. Several studies have examined the prevalence of OSA in patients with POAG and vice versa ii. The prevalence of OSA in patients with POAG or NTG ranged from 20% to as high as 57%. iii. Conversely, studies of patients with OSA have an estimated POAG and NTG prevalence that ranges from 2% to 27% (General population is 2%) iv. The severity of glaucoma was related to the severity of OSA (apnea/hypopnea index as well and RDI) b. Pathophysiology i. Several proposed pathophysiologic mechanisms may link OSA to glaucoma, although most theories have not received adequate scientific testing. ii. Direct hypoxic injury to the nerve iii. Disrupted autoregulation of blood flow to the optic nerve from periods of hypoxia and hypercapnia iv. Disruption of blood flow from periods of hypotension during apneas. v. Some have theorized that increased IOP was associated with apnea c. Treatment i. Lowering IOP 1. Drops 2. Lasers ii. Surgery iii. Neuroprotection? 1. Brimonidine 2. Ca channel blockers- minimal, if any benefit 3. Memantine- failed to prove effective d. Treatment of OSA i. Several studies have shown benefit of CPAP treatment in patients with both OSA and glaucoma Obstructive Sleep Apnea and Other Optic Neuropathies 1. Non-ischemic optic neuropathy a. Sudden painless onset of unilateral visual loss. b. Visual loss is typically irreversible and may deteriorate further during the course of days or weeks. c. Clinical findings include nerve fiber bundle field defects, relative afferent pupillary defect, and optic disc edema d. Pathologyi. Exact pathogenesis is unknown but is believed to be related to vasculopathic occlusion causing infarction. 9

11 ii. microvascular disease iii. optic disc crowding iv. optic disc compartment syndrome v. systemic nocturnal hypotension, and nocturnal hypoxia. e. Relation to OSA i. The risk ratio was 4.9 in patients with OSA compared with the general population f. Mechanism i. impaired optic nerve head blood flow autoregulation secondary to the direct effects of repetitive apneic episodes, apnea-induced blood pressure variations ii. an imbalance between nitric oxide, a vasodilator, and endothelin, a vasoconstrictor. iii. direct hypoxic effects on the optic nerve iv. episodic increases in intracranial pressure (subsequently transmitted to the eye via the cerebrospinal fluid within the optic nerve sheath), associated with hypercapnia during apneic episodes, may act on the optic nerve head either through direct compression or impaired circulation. g. Treatment i. No effective treatment is available for NAION and no studies have shown that treating OSA reduces the risk of NAION 2. Papilledema a. Refers specifically to bilateral optic disc swelling in the setting of increased ICP b. occurs when the elevated ICP is transmitted to the eye through the optic nerve sheath. c. The elevated pressure mechanically disrupts axoplasmic flow within the optic nerve, leading to swelling of the axons and leakage of water, protein, and other cellular contents into the extracellular space d. When a cause of increased ICP cannot be found, it is referred to as idiopathic intracranial hypertension. e. Pathology in relation to OSA i. Studies have found large increases in the ICP during sleep that correlated with apneic events. ii. The degree of increase in ICP correlated with the duration of the apnea and the decrease in oxyhemoglobin saturation. iii. Secondary to transient hypercapnia and the resultant transient increases in ICP. f. Treatment i. Acetazolamide 10

12 ii. Some reports of improvement with CPAP and treatment of OSA 3. Conclusion a. Many optic nerve diseases including glaucoma, NAION and papilledema may be related to OSA. Therefore, testing patients with these findings for OSA may be beneficial as well as having patients with OSA screened for glaucoma and warned about the higher risk of other optic neuropathies. 11

13 References 1. Culbertson WW, Ostler HB. The floppy eyelid syndrome. Am J Ophthalmol 1981;92: Culbertson WW, Tseng SC. Corneal disorders in floppy eyelid syndrome. Cornea 1994;13(1): Van den Bosch WA, Lemij HG. The lax eyelid syndrome. Br J Ophthalmol 1994;78: Ezra DG, Beaconsfield M, and Collin R. Floppy Eyelid Syndrome: Stretching the Limits. Surv Ophthalmol 2010;55: Fowler AM, Dutton JJ. Floppy Eyelid Syndrome as a Subset of Lax Eyelid Conditions: Relationships and Clinical Relevance (an ASOPRS Thesis). Ophthalmic Plastic & Reconstructive Surgery: Ophthal Plast Reconstr Surg 2010;26: Waller EA, Bendel RE, Kaplan J. Sleep disorders and the eye. Mayo Clin Proc 2008;83: Rossiter JD, Ellingham R, Hakin KN, Twomey JM. Corneal melt and perforation secondary to floppy eyelid syndrome in the presence of rheumatoid arthritis. Br J Ophthalmol April; 86(4): Donnenfeld ED, Perry HD, Gibralter RP et al. Keratoconus associated with floppy eyelid syndrome. Ophthalmology 1991;98: Liu DTS, Di Pascuale MA,Sawai J et al. Tear Film Dynamics in Floppy Eyelid Syndrome. Invest Ophthalmol Vis Sci. 2005;46: R Reyniers and D Paridaens. Spontaneous globe luxation and floppy eyelid syndrome in a patient with Hashimoto's disease. Eye (2007) 21, Schlötzer-Schrehardt U, Stojkovic M, Hofmann-Rummelt C et al. The Pathogenesis of Floppy Eyelid Syndrome : Involvement of Matrix Metalloproteinases in Elastic Fiber Degradation. Ophthalmology 2005;112: Alan A McNab. Reversal of floppy eyelid syndrome with treatment of obstructive sleep apnoea.. Clin Exp Ophthalmol 2000;28,: Karger RA, White WA, Park WC et al. Prevalence of Floppy Eyelid Syndrome in Obstructive Sleep Apnea Hypopnea Syndrome. Ophthalmology 2006;113: Burkat CN, Lemke BN. Acquired lax eyelid syndrome: an unrecognized cause of the chronically irritated eye. Ophthal Plast Reconstr Surg Jan;21(1): Olver JM, Sathia PJ, Wright M. Lower Eyelid Medial Canthal Tendon Laxity Grading An Interobserver Study of Normal Subjects. Ophthalmology 2001;108: Leibovitcha I and Selva D. Floppy eyelid syndrome: Clinical features and the association with obstructive sleep apnea. Sleep Medicine. 2006:7; Bouchard CS. Lateral tarsorrhaphy for a noncompliant patient with floppy eyelid syndrome. Am J Ophthalmol. 1992;114(3): Gonnering RS, Sonneland PR. Meibomian gland dysfunction in floppy eyelid syndrome. Ophthal Plast Reconstr Surg. 1987;3(2): Netland PA, Sugrue SP, Albert DM, Shore JW. Histopathologic features of the floppy eyelid syndrome. Involvement of tarsal elastin. Ophthalmology. 1994;101(1):

14 20. Saidel MA, Paik JY, Garcia C, Russo P, Cao D, Bouchard C. Prevalence of Sleep Apnea Syndrome and High-Risk Characteristics Among Keratoconus Patients. Cornea 2012;31: Arthur S, Cantor LB. Update on the role of alpha-agonists in glaucoma management. Exp Eye Res Sep;93(3): Lee D, Kim KY, Noh YH, Chai S, Lindsey JD, Ellisman MH, Weinreb RN, Ju WK. Brimonidine blocks glutamate excitotoxicity-induced oxidative stress and preserves mitochondrial transcription factor a in ischemic retinal injury. PLoS One. 2012;7(10):e Mayama C. Calcium channels and their blockers in intraocular pressure and glaucoma. Eur J Pharmacol Sep 15;739: Osborne NN. Recent clinical findings with memantine should not mean that the idea of neuroprotection in glaucoma is abandoned. Acta Ophthalmol Jun;87(4): Kremmer S, Niederdräing N, Ayertey HD, Steuhl KP, Selbach JM. Obstructive sleep apnea syndrome, normal tension glaucoma, and ncpap therapy a short note. Sleep. 2003;26(2): Mojon DS, Mathis J, Zulauf M, Koerner F, Hess CW. Optic neuropathy associated with sleep apnea syndrome. Ophthalmology. 1998;105(5): Sebastian RT, Johns S, Gibson RA. Treating obstructive sleep apnoea syndrome: does it improve visual field changes [letter]? Eye. 2006;20(1): Mojon DS, Hedges TR III, Ehrenberg B, et al. Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol. 2002;120(5): Lee AG. Three questions on the role of sleep apnea syndrome in optic disc edema [letter]. Arch Ophthalmol. 2001;119(8):