How to Diagnose the Ocular Surface Disease in Treated Glaucoma Patients
a micro-pipette and the patient is asked to blink several times. The TF-BUT is evaluated measuring the interval between a complete blink and the appearance of the first area of tear film break-up on the corneal tear film, using a cobalt blue filter on the slit lamp microscope. The TF-BUT values greater than or equal to 10 seconds are coded as normal and TF-BUT values less than 10 seconds as abnormal.29,30 TF-BUT is usually performed prior to grading.
The
Corneal staining can be determined with different dyes: with fluorescein, staining must be graded as quickly as possible after instillation, since the dye then diffuses rapidly into the tissue and its high luminosity blurs the stain margin; staining after lissamine green, persists at high contrast and may therefore be observed for a considerable period.
The presence of corneal staining can be defined as more than one dot of fluorescein staining over the corneal surface. Since fluorescein diffuses rapidly into tissues, it is to assess staining rapidly, in sequence, in the right and then the left eye, so that the staining patterns observed are equally crisp. Superficial punctate keratitis can be graded according to the corneal fluorescein staining scale by determining the area and density of the lesion on a zero to three scale, where zero indicates the absence of keratitis punctata, one equals mild (a few punctata of staining but less than 10% coverage of the corneal surface; two equals moderate (10–50% coverage of the corneal surface); and three equals severe (more than 50% coverage of the corneal surface [see Figure 3]).31
Lissamine green is available as impregnated strips or may be ordered as a pre-prepared solution. A 1% drop will give more intense staining. Because the drop is well tolerated, no anaesthetic is required. Using white light of moderate intensity, staining at the corneal region and the interpalpebral region of the nasal and temporal conjunctiva is graded using the Oxford Scheme.31
The severity designations used
for lissamine green staining are the following: 0 to I is normal; II to III is mild to moderate; and IV to V is severe (see Figure 4). Since this dye does not diffuse into the substantia propria of the conjunctiva, the staining pattern is retained for longer.
Discussion
Glaucoma is a chronic disease that is often treated with topical drugs. Unfortunately, the chronic use of most IOP-lowering medication is associated with some symptoms of toxicity, such as ocular inflammation, allergy and dry eye. This toxicity has been associated with the preservative BAK, which damages conjunctival and corneal epithelial cells. A recent paper on a rabbit dry eye model induced by topical BAK10 demonstrated that BAK causes damage to the cornea and conjunctiva, decreases tear basal secretion and globlet cell loss and MUC5AC deficiency. Recent studies32–35
pointed out that the exclusive use of
preservative-free eye drops clearly reduces the signs of ocular surface alteration in glaucoma patients and that the use of alternatively preserved glaucoma medications cause minimal adverse effects on the ocular surface compared with drugs with high BAK levels. Despite this, to date, the majority of glaucoma medications are still preserved.
Thygesen et al. in 2000,36 in 2009,16
Costagliola et al. in 200137 and Rossi et al. evaluating prostaglandin analogues in the ocular surface,
1. Report of the International Dry Eye Workshop (DEWS), The definition and classification of dry eye disease, Ocul Surf, 2007;5:75–92.
2. European Glaucoma Society, EGS Terminology and guidelines for
Usually, glaucoma patients undergo several specific and complex tests to evaluate morphology (hormone replacement therapy [HRT], optical coherence tomography [OCT], GDxTM Nerve Fiber Analyzer [GDx]) and function (visual field [VF], pattern electroretinogram [PERG]). Recent literature suggests the impact that an abnormal ocular surface status could have on patients’ wellbeing.16,41
The ocular surface status should
be evaluated regularly before starting a new chronic topical therapy and during the follow-up to ensure the timely detection and treatment of pathological signs on the ocular surface. A misdiagnosed and consequently, untreated dry eye may alter vision. These negative effects should be added to glaucoma’s natural evolution and progression.
In conclusion, a complete ocular examination comprehensive of the ocular surface evaluation should be performed on each glaucoma patient before starting a topical therapy and in the follow-up. The tests suggested in this article to verify the presence of ocular surface alteration are simple, easy to perform and require little time. n
glaucoma, 3rd edition, Savona, Italy: Dogma, 2008:14–21.
3. Guenoun JM, Badouin C, Rat P et al., In vitro study of inflammatory potential and toxicity profile of latanoprost, travoprost, and bimatoprost in conjunctiva-derived epithelial
cells, Invest Ophthalmol Vis Sci, 2005;46:2444–50.
4. Rolando M, Refojo MF, Tear evaporatimeter for measuring water evaporation rate from the tear film under controlled conditions in humans, Exp Eye Res, 1983;36:25–33.
EUROPEAN OPHTHALMIC REVIEW 41
Figure 4: Oxford Grading Scheme Panel
A B C D E >E
Grade
Criteria 0
Equal to or less than panel A
I
Equal to or less than panel B, greater than A
II
Equal to or less than panel C, greater than B
III
Equal to or less than panel D, greater than C
IV V
Equal to or less than panel E, greater than D
Greater than panel E
concluded that prostaglandin analogues were safer on ocular surface function than topical timolol. Pisella and Badouin in 2004,8
compared in
the same conjunctival cell line the pro-apoptotic effects of timolol and latanoprost when associated with the same 0.02% BAK concentration: the decrease in apoptosis and cell viability levels observed with prostaglandin analogue were significantly lower than those induced by preserved timolol.8
Prostaglandin derivatives may have a relative
protective effect against the toxicity of this preservative on conjunctival cells. Okada’s paper on the effects of topical medication evaluated by gene expression patterns6
disagrees with these conclusions: the
mechanism remains to be determined and further investigation on humans are required. Moreover, age13,14
and diabetes1,38–40 represent
risk factors involved in the development of ocular surface disease: glaucoma patients are therefore, presumably at a higher risk for developing ocular surface disease as both diseases are more common in older and in diabetic patients.
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