Glaucoma and other ocular complications in herpetic and HLA-B27 associated anterior uveitis.

Secondary glaucoma is one of the major ocular complications of uveitis. The
prevalence, clinical symptoms and the mechanism of elevated intraocular
pressure vary depending on the cause of the uveitis. The obstruction of the
drainage of aqueous humor may be reversible (for example, by the accumulation
of inflammatory cells into the intertrabecular space, edema of the trabecular
lamellae, or a closed chamber angle by swelling of the ciliary body) or is
irreversible (by, for example scarring). Because glaucoma can lead to a
significant decrease in visual function, it is important to not only evaluate
the inflammatory reaction in patients with uveitis, but also the intraocular
pressure and visual fields.

The standard therapy in anterior uveitis is giving steroid eye drops. In the
beginning, often with a high frequency, depending on the inflammatory activity.
After a week, the inflammatory activity in the anterior chamber has to be
reduced to about half of the number of cells that was seen in the first
presentation. It is important that patients frequently come to the outpatient
clinic to monitor the reduction of the inflammatory activity, and if necessary,
to adjust the treatment. The frequency of the outpatients controls depends on
the severity of the inflammatory activity. If there is no reduction of the
inflammatory activity, a periocular injection of steroids or a course of oral
prednisolone is to consider. It is also advisable to prescribe pupil dilating
eyedrops, such as atropine, until the inflammation has decreased. This to
prevent the formation of posterior synechiae to the iris and to give the iris
more time to recover. There is no standard research on glaucoma. Only when
patients have a high IOP, for a longer period of time, a visual field test
(perimetry) will be performed. Patients with only a few temporary IOP
elevations are usually not examined.

So far there is no consensus on the prevalence of glaucoma in patients with
anterior uveitis based on HLA-B27 positivity. The values **range from 0-19%.
The measured prevalence of temporary IOP increase during active inflammation
varies from 5-21%. The definition of glaucoma, in all these studies differs, or
is missing, so that comparing these numbers is difficult. In these studies it
is indicated that temporary IOP elevations occur during the inflammatory phase,
but it is not mentioned whether this is at presentation or later in the course
of the uveitis, making it difficult to determine whether the IOP rise occurs as
a result of active uveitis, the use of corticosteroids or secondary changes in
the chamber angle (anterior synechiae). It is well known that ocular
hypertension is one of the side effects of corticosteroid eye drops. This
usually occurs after extended use (weeks to months). Furthermore, in the
studies done so far only the prevalence of glaucoma and sometimees the
prevalence of a temporary increase in IOP is stated. They do not look at the
possible damage to the optic disc / visual field defects by temporary IOP
elevations. Also, nothing is mentioned about the duration of the temporary IOP
elevations, anti-glaucomatous medication use, surgical interventions and the
present status.

Also the prevalence of glaucoma in patients with anterior uveitis based on
herpes (HSV and VZV) varies greatly, these numbers are between 2 and 21%. The
reported values **regarding the IOP elevations during active uveitis are quite
similar and vary from 47 to 51%.

With this research we want to determine the prevalence of glaucoma and
temporary IOP elevations in our own anterior uveitis population, with a clear
definition of glaucoma and IOP elevation. We will study two groups of patients,
all with anterior uveitis based on already known HLA-B27 positivity or herpetic
(HSV / VZV) associated anterior uveitis. All patients are or were treated for
uveitis in the UMCG in Groningen. We will study these two groups of patients
because these two forms of anterior uveitis are, in our region, relatively
frequent. It is known that the etiology of uveitis varies between different
ethnic groups and countries, and even between regions in the same country.

After this study we hope to have obtained a better understanding of the course
of IOP elevations and glaucoma in these two groups. We will look at the
prevalence of glaucoma and at a possible relationship between glaucoma and the
number of uveitis episodes and duration of active disease. After this we hope
to know if these patients, even after complete remission of the uveitis, have
to be monitored for a possible development of glaucoma. We also want to know
whether one or more ocular pressure peaks can cause damage to the optic nerve.

In addition to the occurence of IOP elevations and glaucoma, we will also look
at the prevalence of other ocular complications. We will look at the formation
of secondary cataract, posterior synechiae and cystoid macular edema. Also, the
visual acuity will be evaluated. We hope to gain more insight in preventing
ocular complications in these two groups of patients.

The study has a retrospective study design. We will use patients* records to
collect the data. The included patients receive a patient information letter
about the study asking them to participate in the study to evaluate the present
status.We will try, wherever possible, to combine the visit for the study with
a scheduled visit at our clinic.

During the first visit we will investigate in all patients:
• The presence of any other ophthalmic disorder (such as cells in the anterior
chamber and at the endothelium, iristransilluminatic defects of the iris,
pseudoexfoliation, Krukenberg spindle, cataract) by slit lamp examination. To
determine the presence of cataract or pseudoexfoliation, it is necessary to
dilate the pupil with tropicamide.
• IOP measurement (applanation tonometry).
• The thickness of the nerve fiber layer of the retina (by laser polarimetry
(GDx)).
• Visual field defects by perimetry (using Frequency Doubling Technology (FDT)).
• The thickness of the cornea (pachymetry).
• The condition of the retina by using the Optos camera (especially for
capturing any retinal uveitic lesions or any other abnormalities that could
explain visual field defects).

If it turns out that the first performed FDT is abnormal, a second FDT will be
done. Is this one abnormal, then a more extensive perimetry will be performed
by a Humphrey Field Analyzer (HFA). In case of abnormalities, this HFA will be
performed three times. The average of the second and third measurement is a
measure for the amount of detected damage. The patients in which the first or
second FDT is normal, will only visit the clinic once. The patients who will
perform one or more HFA's, have to repeatedly visit the clinic (with a maximum
of three times). If the diagnosis of glaucoma is made**, a gonioscopy will be
performed to view the anterior chamber angle. If a previous pachymetry is
performed, then this needs not be done again. If a patient has performed
perimetry before the start of the study, then we will check how this fits in
our schedule and decide whether additional perimetry is necessary.

Performing an HFA and gonioscopy is standard medical care for glaucoma
patients. We perform this additional testing only in patients who have
indications for glaucoma (two times a positive FDT). If the diagnosis of
glaucoma is made in a patient who is not already known with this, then one of
the supervising ophthalmologists will be consulted about the necessary therapy
and follow-up.

The risk that patients have and the load is minimal. The measurements performed
during the first visit, will be conducted with ophthalmic equipment and are
standard ophthalmological examinations. These measurements bring little risk
and are normally also used in ophthalmic care. If patients have visual field
defects on the FDT corresponding to glaucoma, a more extensive perimetry is
needed. This does not increase the risk for the patient. Furthermore, only in
patients suspected of glaucoma, gonioscopy should be performed. A lens will be
placed on the eye, so we can look at the anatomy of the anterior chamber angle,
this is necessary for making the correct diagnosis. We will anaesthetise the
eye with a drop of Oxybuprocaïne. This examination provides no harm to the
patient and it is a standard examination in patients with glaucoma.