Hara, Shuya*; Kojima, Takashi*; Ishida, Reiko*; Goto, Eiki*; Matsumoto, Yukihiro*; Kaido, Minako*; Shimazaki, Jun*; Dogru, Murat†; Tsubota, Kazuo*
Conjunctivochalasis refers to laxity of the inferior and/or superior bulbar conjunctiva, which may be sandwiched between the eyelids.1–17 Ocular irritation, epiphora, dryness, blurred vision, discharge, ocular fatigue, and subconjunctival hemorrhage are the main reported symptoms of conjunctivochalasis.1–17 The prevalence of conjunctivochalasis has been reported to increase with age.12, 17 Mimura et al.17 reported that varying grades of conjunctivochalasis existed in more than 98% of Japanese older than 60 years in a hospital-based study. A widely accepted grading system for conjunctivochalasis in Japan has been reported by Yokoi and co-workers12 who classified conjunctivochalasis into grades of severity as follows: grade 0, no conjunctivochalasis; grade 1, no conjunctivochalasis with natural blinking, chalasis aggravated after forced blink (height of chalasis less than the height of the tear meniscus); grade 2, chalasis apparent without forced blinks, height less than the height of the tear meniscus; and grade 3, chalasis height higher than the tear meniscus height, apparent without forced blinking.
There is still no agreement regarding the cause of conjunctivochalasis to date. Although some reports described delayed tear clearance and ocular surface inflammation as the pivotal causative factors,2, 3 other reports have suggested that inflammation played a minor role in the pathogenesis.4, 5 Clinical symptoms of conjunctivochalasis have been reported to result from coexisting keratoconjunctivitis sicca, nasolacrimal duct obstruction, and the presence of chalasis occupying the tear meniscus and blocking the drainage route for tears along the lid margin.
The initial step in the management of symptoms in patients with low grades of conjunctivochalasis usually involves instillation of non-preserved artificial tear drops and/or topical steroids. If such medical therapies are not effective, surgical removal of the redundant conjunctiva usually becomes the next treatment option especially in grade 3 conjunctivochalasis with symptoms.6 Several surgical techniques for the treatment of conjunctivochalasis have been reported to improve the clinical symptoms and tear instability.4, 7–11
Tear meniscus plays an important role as a reservoir for tears and as a delivery system for maintenance of a stable tear film on the ocular surface with blinking.18–20 The redundant conjunctiva at the lid margin is believed to not only disturb the integrity of the tear meniscus and induce foreign body sensation and irritation along with other ocular symptomatology but also disrupt the tear film stability as well.4 Tear break-up analysis with fluorescein dye is the most commonly used test of tear stability. Although it is easy to perform, variations in the concentration and pH of the fluorescein solutions, differences in the volume of the instilled drops between different clinical centers, the presence of preservatives and invasiveness of the procedure are the main sources of errors in this method. Research into non-invasive methods resulted in the development of techniques for the assessment of precorneal tear film BUT without the use of fluorescein (non-invasive BUT). Non-invasive BUT using instruments such as the grid xeroscope or tearscopes allowed evaluation of the tear film by eliminating physical disturbance of the film from the instillation of fluorescein, along with the possibility of reflex tearing. Corneal topographical examinations have also been shown to help in the assessment of corneal surface irregularities in aqueous tear deficiency states, by using indices such as surface regularity and asymmetry indices. These indices represent local variations in corneal contour providing invaluable information about the relation of the corneal and tear film status with progression of corneal disease and irregular astigmatism. However, conventional corneal topography examination methods can provide corneal surface data at only one time point. The Tear Stability Analysis System (TSAS) for the Topographic Modeling System (TMS)-2N corneal topography instrument (Tomey Technology, Nagoya, Japan) can take 10 consecutive corneal topograms, one per second for 10 s. TSAS can detect subtle time-wise changes in the tear film deriving data from the distortion of the mire rings. While studying the changes in fluorescein BUT values, vital staining scores, Schirmer test values and symptom scores have been reported to be useful in assessing the efficacy and clinical outcome of surgical treatment for conjunctivochalasis,4, 7–11 this study analyzed the changes in symptoms after surgery for conjunctivochalasis and their association with tear film stability by using a non-invasive technology called as the TSAS and an index named as “break-up index.”
PATIENTS AND METHODS
A total of 15 eyes of 15 patients with grade 3 conjunctivochalasis obliterating the lower tear meniscus were enrolled. This study included 14 females and one male with a mean age of 74.1 ± 5.2 years (range, 63 to 82 years). Conjunctivochalasis was diagnosed under slitlamp examination with fluorescein staining and graded according to Yokoi's grading scale12 by the same observer (S.H.).
None of the participants wore contact lenses or had a systemic disorder or other ocular diseases that would have influenced the measurement of tear functions. Subjects with lid abnormalities, meibomian gland disease, and/or blepharitis were excluded.
Patients with a history of any other ocular surgery or systemic drug use within 6 months before the surgery for conjunctivochalasis were also excluded from the current study. All patients had received preservative-free artificial tear drops containing 0.1% KCl and 0.4% NaCl (Softsantear, Santen Pharmaceutical Co. Ltd., Osaka, Japan) 4 to 10 times daily, 0.1% fluorometholone (Flumetholone 0.1, Santen) 2 to 4 times daily, and/or 0.1% hyaluronic acid (preservation free Hyalein mini 0.1, Santen) 4 to 6 times daily.
Only patients who kept complaining of the subjective symptoms after a medical treatment of at least 8 wk and who opted for surgical treatment were enrolled in this study. None of the subjects showed corneal fluorescein staining under slit lamp examination before the operation.
We strictly adhered to the tenets of the Helsinki Declaration and received full written informed consent from all subjects. Study examination procedures were reviewed by the ethic board.
Surgery for Conjunctivochalasis and Postoperative Care
All surgical treatments were performed as described previously by Yokoi et al.4, 9 Briefly, the lower part of the conjunctiva was divided into nasal, central, and temporal blocks and redundant conjunctiva was resected depending on the redundancy within each block to reconstruct tear meniscus completely from the lateral canthus to the punctum at the lower lid margin.4, 9
Topical anesthetic eye drops using 2% oxybuprocaine (Benoxinate hydrochloride, Santen) and subconjunctival local anesthesia using 1% lidocaine (Xylocaine injection 1%, AstraZeneca K.K., Osaka, Japan) were applied. An arc-like incision of the lower half of the bulbar conjunctiva was made 2 mm apart from the corneal limbus. Subconjunctival tissues were excised distally from the arc-like incision to extend the redundant conjunctiva. Three blocks of redundant conjunctiva separated with radial incision were resected independently according to the extent of redundancy. Interrupted sutures with 8-0 vicryl were placed to close the central block first and the rest of the two blocks were sutured after adjustment of the shape and tension so that the sutured junction between the blocks became smooth without redundancy to obtain a good tear meniscus.
A topical 0.5% levofloxacin (Cravit ophthalmic solution, Santen) and 0.1% fluorometholone eye drops (Flumetholone, Santen) were prescribed to all patients for 1 month after surgery. Stitches were removed 1 week after the surgery.
Assessment of Ocular Symptoms
Symptom questionnaires were administered before and 3 months after surgery. Symptoms including irritation, ocular fatigue, epiphora, dryness, blurred vision, discharge, and subconjunctival hemorrhage were listed on the questionnaire sheet and all patients answered whether they had those symptoms before and 3 months after surgery. Patients were required to select from the following response options including “significantly improved,” “slightly improved,” “no changes,” “slightly worsened,” “significantly worsened,” and “can't say.” Questionnaires were completed by the patients without any assistance from the medical staff.
Assessment of Ocular Surface and Tear Functions
The TSAS uses a software installed in the TMS-2N (Tomey Corporation, Nagoya, Japan) corneal topography device and was developed to non-invasively assess the precorneal tear film break-up time without use of fluorescein.21 TSAS was programmed to capture corneal topographic maps continuously every second for 10 s while the subjects opened both eyes and gazed at a fixed point during the measurement. A total of 11 images are taken, and the tear break-up time at each spot on the topographic map is computerized and added up into one break-up map. A change of corneal power by more than 0.5 D at each spot on the topographic map was indicative of tear break-up (Fig. 1A). Tear break-up changes were assessed by 0.5 D increments, the algorithms of which were set in the analysis software by the developers (Tomey Corporation, Nagoya, Japan). TSAS can automatically calculate the percentage of tear break-up areas by counting the number of points that showed a refractive change >0.5 D comparing the simultaneous measurement points during a 10 s testing. New break-up areas on the topographic map were analyzed at every second, and then shown on a color-code map at the lower right corner of the print-outs as demonstrated in Fig. 1A. A new tear stability index called “break-up time index” (BUI) was calculated by multiplying the ratio of the new break-up areas by the whole corneal area divided by the time factor as shown in Fig. 1B. Eyes were kept open during the measurements and an experienced examiner performed all TSAS measurements obtaining well-focused and properly aligned images of the eyes.
After the TSAS measurements, the standard fluorescein tear film break-up time (FBUT) measurement was performed as reported previously after instillation of 2 μL of 1% fluorescein with preservative-free solution by the same observer. TSAS measurements were performed at least 2 h after instillation of artificial tear drops, to avoid any effects on the tear film stability.
The standard Schirmer I test without topical anesthesia was performed at least 15 min after the FBUT measurement. The sterilized strips of filter paper (Schirmer test paper, Showa Yakuhin Kako Co, Ltd, Tokyo, Japan) were placed in the lateral canthus and left in place for 5 min. These same measurements were performed again 3 months after the surgery in the same order for every patient.
A paired t test was performed for the comparison of BUI, FBUT, and Schirmer I test differences before and 3 months after surgery for conjunctivochalasis. A p < 0.05 was considered as statistically significant. StatView software was used for statistical analysis (Windows 2000; SAS Institute Inc., Cary, NC).
Changes of Symptoms After Surgery for Conjunctivochalasis
All cases had grade 3 conjunctivochalasis preoperatively. All surgeries were performed without any complications, and a complete reconstruction of the tear meniscus from the lateral canthus to the punctum was achieved at the lower lid margin.
Symptoms before surgical treatment in all eyes are shown in Table 1. All patients had more than two symptoms before surgery; however, at least one symptom was observed to improve in 14 patients (93.3%). One patient (6.7%) showed no improvement of symptoms after the surgery. The individual improvement of these symptoms 3 months after surgical treatment is shown in Fig. 2.
Changes of Ocular Surface Findings and Tear Functions After Surgery for Conjunctivochalasis
The mean BUI was 42.8 ± 18.7 (range, 6.4 to 68.5) before surgery, which significantly improved to 60.7 ± 16.5 (range, 23.3 to 79.5) 3 months after surgery (p = 0.0036), as shown in Table 2. Representative anterior segment fluorescein-stained photographs of a 46 year old female subject before and after surgery are shown in Fig. 3A and B. The corresponding pre- and postoperative TSAS findings are shown in Fig. 3C and D. The BUI improved from 57.56 to 74.21 after surgery in this patient. One patient did not have improvement of ocular symptoms after surgery. The TSAS results of this patient before and after surgery are shown in Fig. 4A and B. The BUI before and after surgery were 38.51 and 23.33, respectively, in this patient.
The mean FBUT value before surgery was 5.7 ± 3.2 s (range, 2 to 10 s), which significantly improved to 8.4 ± 2.5 s (range, 2 to 10 s) 3 months after surgery (p = 0.0438), as shown in Table 2.
The mean Schirmer test value was 8.9 ± 6.4 mm (range, 1 to 25 mm) before surgery and 8.7 ± 7.7 mm (range, 1 to 29 mm) 3 months after surgery. There was no significant difference between these values (p = 0.9064), as shown in Table 2.
Conjunctivochalasis has been reported to cause various subjective symptoms such as irritation, epiphora, dryness, discharge, ocular fatigue, blurred vision, and objective findings such as SPK and/or subconjunctival hemorrhage.1–17
Although there is no consensus regarding the cause of conjunctivochalasis, it is generally believed that the obliteration of the lower and/or upper lid margin with the redundant conjunctiva may prevent the formation of a regular tear meniscus, interfering with efficient delivery of tears to the ocular surface and cause undesirable epiphora.1, 2, 4, 7, 13–17
Several reports described the efficacy of surgical reconstruction of the tear meniscus in conjunctivochalasis for improvement of ocular signs and symptoms.4, 7–11 Yokoi et al.4 reported the surgical therapeutic outcome in 168 eyes of patients with conjunctivochalasis, in whom improvement of symptoms after the operation was obtained in 143 eyes (85.1%). However, even if a successful reconstruction of the tear meniscus was obtained in each case with conjunctivochalasis after the surgery, some cases showed significant improvement of symptoms while other cases could not obtain a remarkable improvement.
The efficacy of surgical tear meniscus reconstruction for conjunctivochalasis has previously been analyzed by assessing changes in ocular symptomatology, vital staining scores, and tear quantity. In this study, in addition to these parameters, we used a new software installed in the corneal topography to evaluate the alterations in tear film stability non-invasively.
Kojima et al.21 previously reported new indices using TSAS to evaluate tear film stability according to the time-wise changes of surface regularity and asymmetry index (SAI) of corneal topography and suggested that TSAS would be a suitable tool for the detection of the tear stability changes in patients with mild dry eyes with low staining scores.
Goto et al.22–24 reported that TSAS could detect subtle time-wise changes of tear film instability more sensitively than the conventional FBUT methodology using fluorescein dye. Two parameters were used to evaluate the tear film stability in their report: tear break-up time (TMS-BUT) and tear break-up area (TMS-BUA). TMS-BUT referred to the timing of occurrence of tear break-up in topographic maps. TMS-BUA was defined as the ratio of areas having tear break-up time <5 s to the whole color-code area. The 2007 International Dry Eye WorkShop report cited TSAS to be an objective and non-invasive test of tear stability with a high sensitivity (97.5%) and specificity (62.5%) for tear break-up detection,25 suggesting that TSAS was one of the important measurement methods for the assessment of dry eye diseases.
In this study, we used TSAS technology and used a new tear stability index called the “BUI” which took both the break-up time and area into account at the same time. The mean BUI was observed to improve significantly 3 months after surgery. The mean FBUT value before surgery also improved significantly 3 months after surgery in our study. This report demonstrated for the first time that the surgical reconstruction of tear meniscus provided an objective improvement of the tear film stability in conjunctivochalasis.
On the other hand, the mean Schirmer test value showed no statistically significant differences before and after surgery. The improvement of tear stability without changes in tear quantity of the surgery is interesting. Attainment of a regular tear meniscus with surgery, improvement of tear reservoir in the tear meniscus with adequate provision of “meniscus tear and lipids” to the ocular surface are the possible explanations in relation to the improvement in tear stability. To date, it has not yet been clarified what kind of changes or factors associated with the ocular surface provide an improvement of the subjective symptoms by the surgical treatment for conjunctivochalasis. Yokoi et al. reported symptomatic improvement in 78% of the eyes after surgery in patients with conjunctivochalasis without dry eyes. Symptoms did not change after surgery in 11.8% of the eyes in that report. Twenty-two percent of the eyes with both conjunctivochalasis and dry eye disease did not show any improvement in ocular symptoms after surgery in Yokoi's series. Subjective symptoms improved in 93.3% of eyes with conjunctivochalasis after the surgery in this study. This outcome was almost the same as those of previous reports regarding surgical treatment for conjunctivochalasis.4, 7–11 These results, however, should be viewed with caution in that the current study lacked a control group. Patient answers to symptom questionnaires might have very well involved recall biases or biases resulting from seasonal variations in symptoms might have been present and have had an effect on the results of the current study.
In relation to objective measures of tear stability, both the mean BUI and mean FBUT values in eyes obtaining improvement of the symptoms after surgery showed statistically significant increase after surgery. Only one patient who had aqueous tear deficiency showed no improvement of ocular symptoms after conjunctivochalasis surgery in this report.
It is possible that ocular irritation resulting from the mechanical forces on the redundant conjunctiva associated with blinking may exacerbate or add up to other ocular symptoms especially dryness in presence of tear volume insufficiency. It might be that even if the effect of mechanical forces are eliminated with a successful conjunctivochalasis surgery, the patient may not self-express this improvement while still being bothered by lack of adequate tears on the ocular surface. From Yokoi's and our experience, we would like to point out to the possibility of not attaining sufficient symptomatic improvement in conjunctivochalasis patients who have aqueous deficient dry eye disease.
The role of other factors or symptoms after surgery such as alterations in inflammation and the extent of tear clearance should be investigated in future studies. The current study chose to evaluate symptoms at 3 months after surgery since a previous report by Yokoi et al. reported improved symptoms at 3 months after surgery in patients with conjunctivochalasis who were followed up for an average of 35 months.
It remains a further goal of this study to establish long-term TSAS changes after surgery in a currently ongoing clinical trial. No adverse reactions during or after surgery nor any recurrences of conjunctivochalasis were observed in this series. Because conjunctival surgery results in conjunctival and scleral adhesions, recurrence of conjunctivochalasis is not anticipated and has not been reported in the literature.
In summary, the current study demonstrated the efficacy of TSAS in evaluating the tear stability non-invasively after conjunctivochalasis surgery. BUI appears to be a promising parameter by being non-invasive and providing an objective assessment of tear film stability. Although the number of subjects did not allow a correlation analysis between BUI and symptoms this time, we observed simultaneous BUI and symptom improvements with surgery in each case except one, justifying conduct of further controlled studies in a larger population. Based on our results, we suggest exertion of caution in terms of delivering a comprehensive informed consent to the patients about the possibility of not attaining sufficient symptomatic improvement if they have associated aqueous deficient dry eye disease that may be a cause of disappointment in terms of patient expectations after surgery.
Drs. Hara and Kojima contributed equally to the work and request acknowledgment of joint first authorship.
This paper was presented at the 30th Japan Cornea Congress, February 9–11, 2006, Tokyo, Japan, and at the 2006 ARVO Meeting, April 30 to May 4, 2006, Fort Lauderdale, Florida.
Johnson & Johnson Ocular Surface and Visual Optics Department
Keio University School of Medicine
Shinanomachi 35, Shinjuku-ku
Tokyo 160-8582, Japan
1. Liu D. Conjunctivochalasis. A cause of tearing and its management. Ophthal Plast Reconstr Surg 1986;2:25–8.
2. Di Pascuale MA, Espana EM, Kawakita T, Tseng SC. Clinical characteristics of conjunctivochalasis with or without aqueous tear deficiency. Br J Ophthalmol 2004;88:388–92.
3. Meller D, Li DQ, Tseng SC. Regulation of collagenase, stromelysin, and gelatinase B in human conjunctival and conjunctivochalasis fibroblasts by interleukin-1beta and tumor necrosis factor-alpha. Invest Ophthalmol Vis Sci 2000;41:2922–9.
4. Yokoi N, Komuro A, Nishii M, Inagaki K, Tanioka H, Kawasaki S, Kinoshita S. Clinical impact of conjunctivochalasis on the ocular surface. Cornea 2005;24:S24–S31.
5. Watanabe A, Yokoi N, Kinoshita S, Hino Y, Tsuchihashi Y. Clinicopathologic study of conjunctivochalasis. Cornea 2004;23:294–8.
6. Meller D, Tseng SC. Conjunctivochalasis: literature review and possible pathophysiology. Surv Ophthalmol 1998;43:225–32.
7. Serrano F, Mora LM. Conjunctivochalasis: a surgical technique. Ophthalmic Surg 1989;20:883–4.
8. Meller D, Maskin SL, Pires RT, Tseng SC. Amniotic membrane transplantation for symptomatic conjunctivochalasis refractory to medical treatments. Cornea 2000;19:796–803.
9. Yokoi N, Komuro A, Sugita J, Nakamura Y, Kinoshita S. Surgical reconstruction of the tear meniscus at the lower lid margin for treatment of conjunctivochalasis. Adv Exp Med Biol 2002;506:1263–8.
10. Otaka I, Kyu N. A new surgical technique for management of conjunctivochalasis. Am J Ophthalmol 2000;129:385–7.
11. Yokoi N, Komuro A, Maruyama K, Tsuzuki M, Miyajima S, Kinoshita S. New surgical treatment for superior limbic keratoconjunctivitis and its association with conjunctivochalasis. Am J Ophthalmol 2003;135:303–8.
12. Hirotani Y, Yokoi N, Komuro A, Kinoshita S. [Age-related changes in the mucocutaneous junction and the conjunctivochalasis in the lower lid margins]. Nippon Ganka Gakkai Zasshi 2003;107:363–8.
13. Bosniak SL, Smith BC. Conjunctivochalasis. Adv Ophthalmic Plast Reconstr Surg 1984;3:153–5.
14. Jordan DR, Pelletier CR. Conjunctivochalasis. Can J Ophthalmol 1996;31:192–3.
15. Wang Y, Dogru M, Matsumoto Y, Ward SK, Ayako I, Hu Y, Okada N, Ogawa Y, Shimazaki J, Tsubota K. The impact of nasal conjunctivochalasis on tear functions and ocular surface findings. Am J Ophthalmol 2007;144:930–7.
16. Kheirkhah A, Casas V, Blanco G, Li W, Hayashida Y, Chen YT, Tseng SC. Amniotic membrane transplantation with fibrin glue for conjunctivochalasis. Am J Ophthalmol 2007;144:311–3.
17. Mimura T, Yamagami S, Usui T, Funatsu H, Mimura Y, Noma H, Honda N, Amano S. Changes of conjunctivochalasis with age in a hospital-based study. Am J Ophthalmol 2009;147:171–7.
18. McDonald JE, Brubaker S. Meniscus-induced thinning of tear films. Am J Ophthalmol 1971;72:139–46.
19. Doane MG. Blinking and the mechanics of the lacrimal drainage system. Ophthalmology 1981;88:844–51.
20. Lemp MA, Weiler HH. How do tears exit? Invest Ophthalmol Vis Sci 1983;24:619–22.
21. Kojima T, Ishida R, Dogru M, Goto E, Takano Y, Matsumoto Y, Kaido M, Ohashi Y, Tsubota K. A new noninvasive tear stability analysis system for the assessment of dry eyes. Invest Ophthalmol Vis Sci 2004;45:1369–74.
22. Goto T, Zheng X, Klyce SD, Kataoka H, Uno T, Karon M, Tatematsu Y, Bessyo T, Tsubota K, Ohashi Y. A new method for tear film stability analysis using videokeratography. Am J Ophthalmol 2003;135:607–12.
23. Goto T, Zheng X, Klyce SD, Kataoka H, Uno T, Yamaguchi M, Karon M, Hirano S, Okamoto S, Ohashi Y. Evaluation of the tear film stability after laser in situ keratomileusis using the tear film stability analysis system. Am J Ophthalmol 2004;137:116–20.
24. Goto T, Zheng X, Okamoto S, Ohashi Y. Tear film stability analysis system: introducing a new application for videokeratography. Cornea 2004;23:S65–70.
25. Research Subcommittee of the International Dry Eye WorkShop. Research in dry eye: report of the Research Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007;5:179–93.