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ORIGINAL ARTICLE
Year : 2007  |  Volume : 14  |  Issue : 2  |  Page : 41-45 Table of Contents     

Aqueous humor outflow facility in ocular cicatricial pemphigoid


1 Immunology and Uveitis Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA
2 Glaucoma Service, New England Medical Center, Tufts University, Boston, MA, USA

Date of Web Publication11-Nov-2009

Correspondence Address:
C Stephen Foster
Massachusetts Eye Research and Surgery Institute, 8th Floor, 5 Cambridge Center, Cambridge, MA
USA
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Source of Support: None, Conflict of Interest: None


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   Abstract 

Purpose. It has been reported that glaucoma is more prevalent in ocular cicatricial pemphigoid (OCP) patients as compared to the general population. The majority of OCP patients with glaucoma were in stage III or IV at the time of OCP diagnosis. Therefore, it was hypothesized that the etiology of glaucoma in such patients could be caused by an impairment of the aqueous humor outflow facility in the context of long-standing inflammation. The aim of this study was to determine whether the aqueous humor outflow facility is impaired in OCP patients.
Patients and Methods.
The aqueous humor outflow facility was compared between the following groups: (1) OCP patients with high pressure glaucoma (HPG) (n = 15) to patients with primary open angle glaucoma (POAG) (n = 13) and no history of OCP or chronic cicatrizing conjunctivitis (CCC); (2) OCP patients without a history of HPG (n = 15) to a group of normal individuals (n = 14); (3) OCP patients in stage II, with or without HPG (n = 12), to OCP patients in stage III (n = 25), with or without HPG.
Results.
There was no statistically significant difference in outflow facility between OCP patients with HPG and patients with POAG and no history of OCP, or between OCP patients without HPG and individuals with no history of OCP or glaucoma. The difference in outflow facility between patients in stage II of OCP and those in stage III of OCP was not statistically significant.
Conclusion.
Glaucoma in patients with OCP might not be related to resistance to the aqueous humor outflow facility.

Keywords: glaucoma, outflow facility, ocular cicatricial pemphigoid


How to cite this article:
Daoud YJ, Letko E, Nguyen QD, Soukiasian SH, Samson C M, Sangwan V, Harper SL, Shawkat M, Schuman JS, Foster C S. Aqueous humor outflow facility in ocular cicatricial pemphigoid. Middle East Afr J Ophthalmol 2007;14:41-5

How to cite this URL:
Daoud YJ, Letko E, Nguyen QD, Soukiasian SH, Samson C M, Sangwan V, Harper SL, Shawkat M, Schuman JS, Foster C S. Aqueous humor outflow facility in ocular cicatricial pemphigoid. Middle East Afr J Ophthalmol [serial online] 2007 [cited 2019 Oct 16];14:41-5. Available from: http://www.meajo.org/text.asp?2007/14/2/41/57692

Ocular cicatricial pemphigoid (OCP) is a systemic autoimmune disease characterized by chronic cicatrizing conjunctivitis (CCC). [1] The diagnosis of OCP is made by immunofluorescence studies of biopsied inflamed conjunctiva that demonstrate the deposition of immunoglobulin and/or complement components at the basement membrane zone. Typically, OCP is slowly progressive, starting as chronic conjunctivitis that evolves into subepithelial fibrosis, fornix foreshortening, and symblepharon formation. This process usually takes several years and commonly results in corneal neovascularization and scarring, the ultimate cause of blindness in patients with OCP.

In a previous study, we reported that 26% of OCP patients had developed glaucoma, an increased prevalence compared to the normal population. [2] Because 89% of OCP patients with glaucoma were in stage III or IV at the time of OCP diagnosis, we hypothesized that the etiology of their glaucoma could be related to an impairment of the aqueous humor outflow facility in the context of long-standing inflammation of the conjunctiva, which may extend into the trabecular meshwork and the Schlemm canal, resulting in ocular hypertension and glaucoma.

To further support or refute this hypothesis, we compared the aqueous humor outflow facility between the following groups: (1) OCP patients with high pressure glaucoma (HPG) to patients with primary open angle glaucoma (POAG) and no history of OCP or CCC; (2) OCP patients without a history of HPG to a group of normal individuals; and (3) OCP patients in stage II, with or without HPG, to OCP patients in stage III, with or without HPG.


   Patients and Methods Top


OCP patients (group A and group B)

All individuals with OCP included in this study suffered from CCC. OCP was diagnosed by conjunctival biopsy using immunohistologic techniques. Direct immunofluorescence of the biopsied conjunctiva showed immunoglobulin and/or complement deposition at the epithelial basement membrane zone in all OCP patients. Each individual was treated with at least 1 immunosuppressive agent prior to or at the time of the study. The OCP patients were divided into 2 groups based on the presence (group A) or absence (group B) of HPG. A patient was diagnosed with HPG if an intraocular pressure (IOP) of more than 21 mmHg was recorded at 2 or more instances and at least 1 of the following was present: visual field defect compatible with glaucoma and optic nerve cupping.

Controls (group C and group D)

Patients with POAG and no history of OCP or CCC were included in group C. Each patient diagnosed with POAG had a documented visual field defect and optic nerve cupping compatible with glaucoma. The results of tonography in group C were compared to those of group A.

Normal individuals without a history of glaucoma, OCP, and CCC were included in group D. Tonography measurements of patients in this group were compared to those in group B.

Gonioscopy was performed in each individual participating in this study. None of the patients or controls underwent cataract surgery and/or intraocular lens (IOL) implantation less than 9 months prior to tonography.

Activity of OCP

Based on the conjunctival injection as previously described, the activity of OCP was graded at the time of tonography. [1] A single observer (CSF) graded the degree of disease activity in each eye (ie, conjunctival injection), using a scale of 0 to 4 in increments of 0.5 at monthly intervals. Other causes of conjunctival inflammation, such as trichiasis, dry eye, or ectropion, were eliminated.

Stage of OCP

The stage of OCP was evaluated according to the previously published staging system for OCP. [1] Briefly, stage I is characterized by chronic conjunctivitis with subepithelial conjunctival fibrosis, stage II by foreshortening of conjunctival fornices, and stage III by the presence of a symblepharon. Stage IV is the end stage of OCP and is distinguished by a dry eye with keratinization of the cornea and ankyloblepharon.

Tonography

Goldmann applanation tonometry and pneumatonography were performed, and the IOP and the outflow facility (C55), respectively, were recorded. The initial IOP over coefficient of outflow facility (Po/C55) was calculated for each individual.

Statistical analysis

A two-tailed Student's t test was used to examine the statistical significance of differences between the 2 groups.


   Results Top


OCP patients with POAG (group A)

Group A included 15 patients (25 eyes) diagnosed with OCP and HPG [Table 1]. The mean age of patients in group A was 76.7 years (range, 50-90 years), and the male to female ratio was 1:2. At the time of tonography, 8 eyes were in OCP stage II and 17 eyes were in OCP stage III. The mean disease activity was 0.32 (range, 0-1.5). Each patient was treated for glaucoma with at least 1 topical agent. None of the patients underwent laser surgery or a surgical procedure for glaucoma. As determined by gonioscopy, 2 patients had rare peripheral anterior synechiae, with angles open to the ciliary body. The mean IOP was 17.6 mmHg (range, 13-24mmHg). Decreased outflow facility was found in 10 eyes (C55<0.12). Borderline outflow facility (0.12-0.20) was detected in 11 eyes, and the remaining 4 eyes had normal outflow facility (C55>0.20). The mean outflow facility (C55) in group A was 0.16 (range, 0.04-0.93). An elevated Po/C55 value (th > 100) was calculated in 17 eyes; it was normal (<100) in 8 eyes. The mean Po/C55 value in group A was 144.3 (range, 71-311).

OCP patients without POAG (group B)

Group B included 15 OCP patients (25 eyes) without HPG [Table 2]. The mean age of patients in group B was 70.5 years (range, 51-90 years), and the male to female ratio was 3:2. At the time of tonography, 7 eyes were in OCP stage II and 18 were in OCP stage III. The mean disease activity was 0.14 (range, 0-0.5). As determined by gonioscopy, 2 patients had peripheral anterior synechiae, with angles open to the ciliary body. The mean IOP was 14.7 mmHg (range, 9-21 mmHg). Decreased outflow facility (C55) was present in 3, borderline in 7, and normal in 15 eyes. The mean outflow facility in group B was 0.25 ± 0.10 (range, 0.08-0.47). An elevated Po/C55 was found in 7 eyes of group B. The remaining 18 eyes of group B had normal Po/C55 values. The mean Po/C55 value was 89.4 (range, 13.0-176.7) in group B.

Patients with POAG (group C)

Group C included 13 patients (25 eyes) with POAG and no history of OCP or CCC. The mean age was 67.9 years (range, 55-80 years), and the male to female ratio was 8:5. The mean IOP was 22.1 mmHg (range, 15-34 mmHg). Decreased outflow facility was found in 13, borderline in 7, and normal in 5 eyes. The mean outflow facility value in group C was 0.15 (range, 0.03-0.56). An elevated Po/C55 was found in 19 eyes. The remaining 6 eyes in group C had normal Po/C55 values. The mean Po/C55 value in group C was 159.1 (range, 40.9-344).

Normal individuals (group D)

Group D included 14 normal individuals (25 eyes). The mean age was 58.1 years (range, 37-75 years), and the male to female ratio was 3:4. The mean IOP was 18.3 mmHg (range, 9-23 mmHg). Decreased outflow facility was present in 1, borderline in 9, and normal in 15 eyes. The mean outflow facility in group D was 0.25 (range, 0.10-0.38). An elevated Po/C55 was found in 5 eyes. The remaining 20 eyes in group D had normal Po/C55 values. The mean Po/C55 value in group D was 82.6 (range, 41.9-130).

OCP patients in stage II

Of 12 patients, 15 eyes were in stage II of OCP. The mean age of OCP patients in stage II was 71 years (range, 51-90 years), and the male to female ratio was 5:7. The mean IOP was 16.3 mmHg (range, 9-24 mmHg). Decreased outflow facility was present in 6, borderline in 6, and normal in 3 eyes. The mean outflow facility was 0.16 (range, 0.05-0.33). An elevated Po/C55 was calculated in 9 eyes. The remaining 6 eyes had normal Po/C55 values. The mean Po/C55 value in stage II of OCP was 134.3 (range, 37.1-311).

OCP patients in stage III

Of 25 patients, 35 eyes were in stage III of OCP. The mean age of OCP patients in stage III was 71.9 years (range, 49-90 years), and the male to female ratio was 1:1. The mean IOP was 16.1 mmHg (range 9-24 mmHg). Decreased outflow facility was detected in 7, borderline in 12, and normal in 16 eyes. The mean outflow facility was 0.22 (range, 0.08-0.93). An elevated Po/C55 was calculated in 15 eyes. The remaining 20 eyes had normal Po/C55 values. The mean Po/C55 value in stage III of OCP was 109.3 (range, 13-325). The clinical profiles of patients in each group are summarized in [Table 3].

Statistical analysis

The two-tailed Student's t test did not reveal a statistically significant difference in outflow facility (C55) between OCP patients with HPG (group A), and patients with POAG and no history of OCP (group C) (P = .794); or between OCP patients without HPG (group B), and individuals with no history of OCP or glaucoma (group D) (P = .952). There was no statistically significant difference in outflow facility between patients in stage II of OCP and those in stage III of OCP (P = .129). The differences in the Po/C55 values between groups A and C (P = .552), between groups B and D (P = .545), and between OCP patients in stage II and stage III (P = .258) did not attain statistical significance [Table 4]. The power of this study to detect a difference of 0.04 units in C55 value was 17%.


   Discussion Top


Ocular cicatricial pemphigoid is a systemic autoimmune disease characterized by CCC. If untreated or treated suboptimally, the conjunctival scarring can progress from subepithelial fibrosis (stage I) to fornix foreshortening (stage II), symblepharon formation (stage III), and ankyloblepharon (stage IV). This process of progression typically occurs over several years.

The prevalence of glaucoma in patients with OCP is greater than that of the general population. We measured outflow facilities using tonography in an attempt to investigate the etiology of glaucoma in patients with OCP. There was no statistically significant difference between outflow facility in patients with OCP and HPG compared to patients with POAG, and there was no statistically significant difference between outflow facility in patients with OCP compared to normal individuals. Furthermore, there was no statistically significant difference between outflow facility in patients with OCP in stage II and those in stage III. These data, therefore, do not support our hypothesis that glaucoma in patients with OCP is related to resistance to the aqueous humor outflow facility.

Several alternative explanations are possible. For example, the hypothesis could be correct, but tonography was not sensitive enough to determine the quantitative difference between outflow facility in the groups tested. We find no statistically significant difference in aqueous humor outflow facility between patients in OCP stage II and those in OCP stage III. This finding suggests that either the amount of conjunctival scarring and disease duration do not play a role in compromising outflow facility in eyes affected by OCP, or that the tonography is incapable of detecting such a role. Alternatively, it is possible that some patients with OCP are genetically predisposed to glaucoma. The fact that 89% of patients with OCP and glaucoma were diagnosed with glaucoma on average 11 years prior to the diagnosis of OCP supports this possibility.

A previous study showed that 2.5% of the normal population (ie, without POAG) may have abnormal aqueous humor outflow facility. [5] Interestingly, we found abnormal outflow facility in 10 (40%) of 25 eyes with OCP and no history of glaucoma. Because individuals with abnormal tonography readings have previously been found to be at a higher risk for developing glaucoma later in life, our observations emphasize the importance of close monitoring of IOP in patients with OCP. In summary, the results of this study do not support our original hypothesis that the etiology of glaucoma in OCP is related to increased resistance to aqueous humor outflow facility. Larger cohorts of patients will be needed to confirm or refute this hypothesis, and to determine the etiology of glaucoma in OCP.

Acknowledgements: The authors would like to thank Mary Ann Beaton for her technical expertise and William Christen for his help with the statistical analysis.

Yassine Daoud is the recipient of the Doris Duke and Harvard Medical School PASTEUR Clinical Research Fellowship.

 
   References Top

1.Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc 1986;84:527-663.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Tauber J, Melamed S, Foster CS. Glaucoma in patients with ocular cicatricial pemphigoid. Ophthalmology 1989;96:33-37.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Heiligenhaus A, Shore JW, Rubin PA, Foster CS. Long-term results of mucous membrane grafting in ocular cicatricial pemphigoid. Implications for patient selection and surgical considerations. Ophthalmology 1993;100:1283-1288.  Back to cited text no. 3      
4.Langham ME, Leydhecker W, Krieglstein G, Waller W. Pneumatonographic studies on normal and glaucomatus eyes. Adv Ophthalmol 1976;32:108-133.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Stamper RL, Lieberman MF, Drake MV, eds. Becker-Shaffer's Diagnosis and Therapy of the Glaucomas. St. Louis, MO; CV Mosby; Yr:76-84.  Back to cited text no. 5      



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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