Supplemental material to be listed online
I. Questionnaires and Surveys to Quantitate Dry Eye Symptoms
The McMonnies questionnaire employs 14 questions that focus on factors associated with dry eye and was designed for use in clinical care. The survey assesses age, gender, contact lens history, dry eye symptoms (soreness, scratchiness, dryness, grittiness, burning), previous dry eye treatments, secondary symptoms (associated with environmental stimuli), medical conditions associated with dry eye syndrome (arthritis, Sjögren syndrome, thyroid disease), dryness of mucous membranes (mouth, throat, chest, or vagina), and medication use.Scores are tabulated using a weighted point assignment to give an overall Index score (0 to 45, higher scores more indicative of dry eye), and a cut-point of greater than 14.5 is recommended for a dry eye diagnosis.The instrument (and scoring key) has been published for use in clinical care and takes approximately 10 minutes to complete and score.[1-5]
The Ocular Surface Disease Index (OSDI) is a 12-item questionnaire designed as a screening survey that assesses symptoms and their impact on vision-related functioning. [6] The instrument, developed by Allergan, Inc.(Irvine, CA) has been the most widely utilized survey in clinical dry eye research and clinical trials, and also possibly the most accepted in clinical care as a validated instrument. There are three subscales: Vision-Related Function, Ocular Symptoms (sensitive to light, gritty, painful or sore, blurred vision, poor vision), and Environmental Triggers. The survey is scored on a scale of 0 to 100, with higher scores representing greater disability. The survey is available online and takes minutes to complete and score. A recent publication by Miller et al. described standard cut-points for the overall OSDI score: normal (0-12 points), mild dry eye (13-22 points), moderate dry eye (23-32 points), and severe dry eye (33-100 points), and also reported that a clinically meaningful change in score ranged from 4.5 to 7.3 points for mild or moderate disease and from 7.3 to 13.4 points for severe disease.[7] The OSDI has been administered to Sjögren’s patients, although no statistically significant difference between Sjögren’s and non-Sjögren’s dry eye subjects was found.
The SPEED questionnaire (Standard Patient Evaluation of Eye Dryness questionnaire)was developed by Korb et al. to be a rapid survey to assess symptoms in clinical practice.[8] This brief survey consists of three areas of questioning: the type of symptoms and the time frame of occurrence (at this visit, within the last 72 hours, within the last 3 months), the frequency of symptoms, and the severity of symptoms. The four symptom groupings are: 1) dryness, grittiness, or scratchiness; 2) soreness or irritation; 3) burning or watering; and 4) eye fatigue. In addition, eye drop use is evaluated. This survey was the first to have specific time reference points. Studies using this instrument with Sjögren’s patients have yet to be done.
The Symptom Assessment in Dry Eye (SANDE) survey also has unique properties in that it utilizes a 100 mm horizontal visual analog scale (VAS) to quantify the frequency and severity of symptoms of dry eye syndrome (DES).[9] A central anchor point representing the last visit demarcates a reference point for the patient to determine worsening or improving symptoms. It was designed to detect differences over time or with treatment, although further refinement and testing in large samples, as well as in Sjögren’spatients is warranted.
The Impact of Dry Eye on Everyday Life (IDEEL) survey was developed in 2005to address concerns related to the impact of dry eye on daily living and quality of life (QoL), [10] The survey contains 3 modules; symptom bother (SB), quality of life, and treatment satisfaction. The validity of the instrument has been assessed by comparing it to generic quality of life instruments. The authors report that the disease-specific IDEEL scales are better able to discriminate between severity levels than the majority of the generic QoL scales and that preliminary evidence demonstrates that the IDEEL will be sensitive to QoL changes over time. The instrument was assessed in patients with Sjögren syndrome, yet controlled longitudinal studies are still needed. In addition to validation, the 20-item IDEEL-symptom bother module has been assessed for clinically meaningful differences. Fairchild et al. reported that ROC results show that a 12-point change in IDEEL-SB is associated with a clinically significant change in symptoms.
1. McMonnies CW, Ho A. Patient history in screening for dry eye conditions. J Am OptomAssoc 1987;58:296-301.
2. McMonnies CW. Key questions in a dry eye history. J Am OptomAssoc 1986;57:512-517.
3. McMonnies CW, Ho A. Responses to a dry eye questionnaire from a normal population. J Am OptomAssoc 1987;58:588-591.
4. McMonnies C, Ho A, Wakefield D. Optimum dry eye classification using questionnaire responses. AdvExp Med Biol 1998;438:835-838.
5. Nichols KK, Nichols JJ, Mitchell GL. The reliability and validity of McMonnies dry eye index. Cornea 2004;23:365-371.
6. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol 2000;118:615-621.
7.Miller KL, Walt JG, Mink DR, Satram-Hoang S, Wilson SE, Perry HD, Asbell PA, Pflugfelder SC. Minimal clinically important difference for the ocular surface disease index. Arch Ophthalmol;128:94-101.
8. Blackie CA, Soloman JD, Scaffidi RC, Greiner JV, Lemp MA, Korb DR: The relationship between dry eye symptoms and lipid layer thickness. Cornea 2009;28:789-94.
9.Schaumberg DA,Gulati A,Mathers WD,et al. Development and validation of a short global dry eye symptom index. Ocul Surf. 2007 Jan;5(1):50-7.
10. Begley CG, Caffery B, Chalmers RL, Mitchell GL. Use of the dry eye questionnaire to measure symptoms of ocular irritation in patients with aqueous tear deficient dry eye. Cornea 2002;21:664-670.
II. Summary of Available Over-the-Counter Tear Supplements
Major Component (s)StrengthTrade NamePreservatives
Carboxymethylcellulose0.5%Refresh Tears Purite
(CMC)0.5%Refresh PlusNone
1.0%Refresh LiquigelPurite
1.0%Refresh CelluviscNone
0.25%GenTeal Gel Drops Na perborate
0.25%TheraTearsNa perborate
CMC/Glycerin 0.5%Optive Purite
0.9%Optive SensitiveNone
Glycerin0.3%Moisture Eyes BAK
HPMC0.2%GenTeal mild SP
0.3%GenTeal moderate SP
0.3%GenTeal GelSP
HPMC/Dextran 700.3%/0.1%Bion TearsNone
0.3%/0.1%Tears Naturale FreeNone
0.3%/0.1%Tears RenewedBAK
HPMC/glycerin/0.3%/0.2%/ Tears Naturale Polyquaturnium-1
Dextran 700.1%Forte
HPMC/Glycerin0.2%/1%Visine TearsBAK
Long Lasting
Clear Eyes Sorbic acid/EDTA
HPMC/Glycerin/ 0.36%/0.2%/Visine TearsBAK
PEG-4000.2%Visine Pure TearsNone
Hypromellose/carbomer 9800.3%Systane Lubricating Na perborate
Gel
Polyvinyl Alcohol(PVA)1.4%AKWA TearsBAK
PVA/PEG-4001%/1% HypoTearsBAK
Glycerin/ Propylene Glycol 0.6%/0.6%Soothe LubricantEDTA
Eye Drops
Propylene Glycol/0.3%/0.4%SystanePolyquad
PEG-400Systane PFNone
Propylene Glycol0.6%Systane Balance
PEG-400/hyaluronate0.25% BlinkTears Na Chlorite
Hyaluronate 0.25%Blink Gel Tears
Oasis Tears Plus
Mineral oil/light mineral oil 0.5%/0.5% Retaine
OINMENTSINGREDIENTS
AKWA Tears OintmentWP^ 85% MO* 15%
2% liquid lanolin
Genteal PM Ointment WP 85% MO 15%
Duratears Ointment Liquid Lanolin MO
Preserved methylparaben 0.05% propylparaben o.01%
HypoTears Ointment WP 85%MO 15%
Tears Renewed Ointment WP 88%MO 12%
Refresh Lacri-lube S.O.P.WP 56.8%MO 42.5% Chlorbutanol 0.5%
Lanolin alcohols
Refresh P.M. WP 57.3%MO 42,5%Lanolin alcohols
preservative free
Tears Again Eye Ointment WPMO (% not specified)
^ WP=white petrolatum *MO=mineral oil
III. Summary Information on Essential Fatty Acids
Sources of EFA:
—Omega 6Omega 3
—Vegetable oilsFish (marine)
—SoybeansFlax seed oil
—Palm oil
—Sunflower seed
—Evening primrose
Evidence for efficacy in treatment of dry eye
The evidence that EFA are useful to treat dry eye disease is sparse. The evidence-based information available to date is in animal studies [1-5] and through clinical trials using omega 6 [6-9], omega 6 + 3 [10,11], and lastly omega 3 [12,13] EFA.
Summary of essential fatty acid research to date:
Animal studies have utilized omega 3 combined with omega 6 and omega 3 alone and all suggested improved signs of dry eye. Some clinical trials with omega 6, lasting 1 to 6 months, showed improved symptoms (Table ). Two clinical trials of combined omega 3 + 6 showed no change in symptoms, while one showed significant improvement in symptoms. Four studies of omega 3 supplementation showed improved symptoms. One epidemiologic study suggested high omega 3 intake, such as eating tuna fish, was correlated with less risk of dry eye disease. Nearly all the research trials have been small studies, not powered to provide definitive proof of efficacy and typically were performed at one site, with a variety of supplements used: omega 6 alone, omega 6 in combination with omega 3, or omega 3 alone. There has been no consistency in the improvement of signs or symptoms, although the data does suggest the value of further study. Current research is underway to develop the best evidence utilizing a randomized controlled trial of omega 3 in well defined dry eye subjects and hopefully there will soon be definitive information to share with clinicians and patients to help them decide on this treatment.
Clinical trials of Omega 3 and 6 EFA
Author/year / N / Design / Length of Rx / ResultOmega 6
Barabino/2003 / 26 / RCT, one site / 45 days / Improved Sx, decrease HLA DR, unchanged Sch and TBUT
Aragona/2005 / 40 / RCT, one site / 1 mo / Improved Sx, unchanged Sch and TBUT
Kokke/2008 / 76 / RCT, cl users / 6 mo / Improved Sx and tear meniscus, no other change in Sg
Querques/2008 / 80 / RCT, s/p PRK / 1 mo / Improved Sch and less corneal staining
Omega 3 and 6
Creuzat/2006 / 71 / RCT, one site / 6 mo / No change in Sx, non-significant change in Sg
Garcher/2009 / 138 / RCT MGD / 3 mo / No change in Sx or Sg, reduced HLA DR
Sheppard/2013 / 38 / RCT KCS / 6 mo / Improved Sx, decreased SAI and HLA DR
Omega 3
Wojtowicz/2011 / 36 / RCT, one site / 3 mo / Improved OSDI, no change in Sg (except Sch)
Macsai/2008 / 38 / RCT, MGD / 1 yr / Improved OSDI
Papas/2007 / 41 / RCT, SS / 3 mo / Improved Sx, increased salivary flow
Penheiro/2007 / 38 / RCT, SS / 6 mo / Improved OSDI and signs
Miljanovich/2005 / 1500 / Epidemiologic / N/A / High omega 3 assoc with less DED, high 6/3 risk for DED
1. Viau S, Maire MA, Pasquis B, Grégoire S, Acar N, Bron AM: Efficacy of a 2-month dietary supplementation with polyunsaturated fatty acids in dry eye induced by scopolamine in a rat model.
Graefes Arch ClinExpOphthalmol; 2009; 247(8):1039-50.
2. He J, BazanHE. Omega-3 fatty acids in dry eye and corneal nerve regeneration after refractive surgery. Prostaglandins LeukotEssent Fatty Acids 2010; 82(4-6):319-25.
3. Li N, He J, Schwartz CE, Gjorstrup P, Bazan HE. Resolvin E1 improves tear production and decreases inflammation in a dry eye mouse model.
J OculPharmacolTher;2010; 26(5):431-9.
4. Dartt DA, Hodges RR, Li D, Shatos MA, Lashkari K, Serhan CN. Conjunctival goblet cell secretion stimulated by leukotrienes is reduced by resolvins D1 and E1 to promote resolution of inflammation. J Immunol.2011; 186(7):4455-66.
5. Barabino S, Rolando M, Camicione P, Ravera G, Zanardi S, Giuffrida S, et al: Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Cornea 2003; 22(2):97-101. [level III]
6. Aragona P, Bucolo C, Spinella R, Giuffrida S, Ferreri G. Systemic omega-6 essential fatty acid treatment and pge1 tear content in Sjögren's syndrome patients. Invest Ophthalmol Vis Sci.2005; 46(12):4474-9. [level III]
7. Kokke KH, Morris JA, Lawrenson JG. Oral omega-6 essential fatty acid treatment in contact lens associated dry eye. Cont Lens Anterior Eye;2008; 31(3):141-6. [level III]
8. Querques G, Russo V, Barone A, Iaculli C, Delle Noci N. Efficacy of omega-6 essential fatty acid treatment before and after photorefractive keratectomy [Article in French]. J Fr Ophtalmol 2008;31(3):282-6.
9. Creuzot C, Passemard M, Viau S, Joffre C, Pouliquen P, Elena PP, et al: Improvement of dry eye symptoms with polyunsaturated fatty acids [Article in French]. J Fr Ophtalmol; 2006;29(8):868-73. [Level III]
10. Wojtowicz JC, Butovich I, Uchiyama E, Aronowicz J, Agee S, McCulley JP. Pilot, prospective, randomized, double-masked, placebo-controlled clinical trial of an omega-3 supplement for dry eye.Cornea; 2011;30(3):308-14.[level II]
11. Macsai MS. The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:336-56. [level II]
12. Pinheiro MN Jr, dos Santos PM, dos Santos RC, Barros Jde N, Passos LF, Cardoso Neto J.Oral flaxseed oil (Linumusitatissimum) in the treatment for dry-eye Sjögren's syndrome patients [Article in Portugese].Arq Bras Oftalmol;2007;70(4):649-55.
13. Miljanović B, Trivedi KA, Dana MR, Gilbard JP, Buring JE, Schaumberg DA. Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women. Am J ClinNutr;2005;82(4):887-93. [level III]
14. Sheppard JD Jr, Singh R, McClellan AJ, Weikert MP, Scoper SV, Joly TJ, Whitley WO, Kakkar E, Pflugfelder SC. Long-term Supplementation With n-6 and n-3 PUFAs Improves Moderate-to-Severe KeratoconjunctivitisSicca: A Randomized Double-Blind Clinical Trial. Cornea.2013 Jul 23; [Epub ahead of print] [level III]
Suggestions with regard to management include nutritional goals: healthy diet with more balanced intake of omega 6 and omega 3. For now, follow the recommendations of the American Heart Association [1]:
Population / RecommendationPatients without documented coronary heart disease (CHD) / Eat a variety of (preferably fatty) fish at least twice a week. Include oils and foods rich in alpha-linolenic acid (flaxseed, canola and soybean oils; flaxseed and walnuts).
Patients with documented CHD / Consume about 1 g of EPA+DHA per day, preferably from fatty fish. EPA+DHAin capsule formcould be considered in consultation with the physician.
Patients who need to lower triglycerides / 2 to 4 grams of EPA+DHA per day provided as capsules under a physician’s care.
1.
IV. Methods of Punctal Occlusion
Temporary punctal occlusion:
Collagen plugs, short-acting that can last for less than a week or longer acting plugs that will not degrade for 4- 6 months can be placed into the punctum and are lodged in the upper or lower canaliculus. They are inserted into the punctum with jewelers forceps and then gently pushed into the canaliculus. The use of these plugs enables one to access whether or not more permanent occlusion might be beneficial in relieving the subjective and objective findings associated with the dry eye condition. It also enables one to determine if epiphora occurs as a complication of the procedure. Temporary punctal occlusion can also be achieved by suturing the punctum closed or by the use of cyanoacrylate glue to close the punctum. Silicone plugs can be used to obtain longer lasting punctal occlusion. This type of punctal occlusion will last as long as the plug remains in place but the physician can remove the plugs at any time. The plugs are available in different sizes; the largest plug that fits the punctum possible should be utilized. The plug is inserted, usually after gently dilating the punctum, into the punctum with the top of the plug being flush with the margin of the eyelid. A potential complication is the insertion of the entire plug into the canaliculus. Furthermore, if the plug is not flush with the eyelid, conjunctival and or corneal irritation can occur. There is also the possibility of spontaneous extrusion of the plug. Balaram and coworkers reported that the estimated probability of plug retention after 6 months was 63%. [1]The loss of the plug was most common in the first 3 months after insertion and the upper plugs had a greater risk of loss compared to the lower ones. In addition, when a loss plug was replaced, it was twice as likely to be extruded compared to placement of the original punctum plug. [1]Horwath-Winter and coworkers reported a retention rate of 69.5% after one year and 55.8% after two years.[2] A rare complication of silicone plugs is its migration into the naso-lacrimal drainage system resulting in canaliculitis or dacryocystitis.
Punctal occlusion can also be achieved by inserting a thermolabile polymer into the punctum. The polymer changes its shape from a rigid solid to a soft gel in response to temperature changes in the local environment. The material is a rigid rod at room temperature; the rod (0.4mm in diameter) is inserted into the punctum with forceps ( 2/3 of its length); after being inserted into the punctum, the material changes shape by expanding to fit and conform to the size of the punctum (from 0.4mm up to 1.0mm) as a result of the temperature in the punctum. As it expands it also decreases in length and its final position is completely contained in the punctum. These have been reported to be as clinically effective as silicone plugs.[3,4] The plug can be removed by irrigation through the lower punctum. However, there are complications associated with this type of punctal occlusion. Spontaneous plug loss has been reported in 2.2% of patients[1] Canaliculitis (prevalence of 7.23% has been reported) and acute dacryocystitis have been reported. [5] Irrigation usually resolved the problems but the plug could also be dislodged causing permanent obstruction requiring dacryocystorhinostomy (DCR).[6]
Permanent punctal occlusion:
This can be achieved by thermo or electro- cauterization of the outflow system. The medial area of the lid is anesthetized with local injection of lidocaine. The cautery or hyfrecator tip is inserted through the puncta and into the canaliculus and the area is treated until one obtains a blanching above the treated area. It is usually prudent to treat one punctum at a time and observe the therapeutic response before any additional punctum is closed. The effect can also be achieved by the Argon laser treatment of the punctum. There is a higher incidence of recanalization with Argon laser treatment.
Punctal occlusion has been shown to improve Schirmer results, tear break-up time,ocular surface staining [7, 8] and visual acuity. [9]However punctal occlusion, at least in normal individuals, can decrease corneal sensation, tear production and tear clearance for 2-3 weeks.[10] Thus there is the theoretical possibility that in patients with significant ocular inflammation, punctal occlusion could exacerbate the condition by retaining inflammatory mediators in the tear film and on the ocular surface.
1. Balaram M, Schaumberg DA, Dana MR. Efficacy and tolerability outcomes after punctal occlusion with silicone plugs in dry eye syndrome. Am J Ophthalmol. 131(1): 30-6, 20017
2. Horwath-Winter J. Thaci A, Gruber A, Boldin I. Long-term retention rates and complications of silicone punctal plugs in dry eye. Am J Ophthlmol. 144(3) 441-444, 2007
3. Burgess PI, Koay P, Clark P. SmartPlug versus silicone punctal plug therapy for dry eye: a prospective randomized trial. Cornea 27(4) 391-4,2008
4. Chen SX, Lee GASmartPlug in management of severe dry eye syndrome. Cornea 26(5) 534-8,2007
5. Hill RH 3rd, Norton SAW, Bersani TA. Prevalence of canaliculitis requiring removal of SmarPlugs.OphthalPlastreconstr Surg. 25(6) 437-9,2009
6. SmartPlug Study Group. Management of complications after insertion of the SmartPlugpunctal plug: a study of 28 patients. Ophthalmology. 113(10) 1859e2-6, 2006
7. Dursun D, Ertan A, Bilezikci B etal Ocular surface changes in keratoconjunctivitissicca with silicone punctum plug occlusion. CurrEye Res: 26 (5): 263-9,2003
8. Altan-Yaycioglu R, Gencoglu EA, Akova YA etal. Silicone versus collagen plugs for treating dry eye: results of a prospective randomized trial including lacrimal scintigraphy. Am J Ophthalmol. 140(1) 88-93, 2005