Behçet’s disease (BD) is a chronic inflammatory, multisystem disorder that was first reported in 1930s by the Turkish dermatologist H Behçet [
Ocular involvement in the form of chronic relapsing-remitting anterior and/or posterior uveitis has been reported in 60%–80% of patients with Behçet’s disease, with more male predilection in the Middle East, with a reported ratio of 2 : 1, and the tendency of the disease to be more severe in the affected males as compared to the female patients [
Different treatment modalities have been proposed for controlling the ocular involvement and vision threatening complications in BD patients, whereas corticosteroids remain the cornerstone for treatment in the majority of cases. Moreover, the use of immunosuppressive drugs has been advocated in selected cases, which might result in controlling the disease process and inducing long term remissions [
The systemic use of these drugs carries the risk of systemic side effects and hence the postulation of intravitreal approach as well as the periocular route of administration in cases with ocular involvement, aiming at direct delivery of the drug to the target organ at a satisfactory concentration as well as avoiding systemic side effects of the drug [
Methotrexate (MTX) is an antimetabolite that was proposed at low doses for the treatment of rheumatoid arthritis (RA) and ocular inflammatory conditions with satisfactory results [
Intravitreal MTX was first introduced for the treatment of recurrent intraocular lymphoma, which was noticed to induce prolonged local remission of ocular disease even with an aggressively growing tumor, with subsequent use in cases with chronic inflammatory ocular conditions [
In the current study, the efficacy of intravitreal methotrexate in controlling posterior segment involvement and inducing remission in BD patients, compared to retro bulbar steroids injection, was evaluated.
The study was done in accordance with the ethical standards of the Declaration of Helsinki 1964 [
In this cross-sectional nonrandomized comparative study, 31 adult BD male patients aged 22–45 years (
A full history taking including the disease manifestations, duration of the disease, and previous medications received, as well as current medications, was taken for all participants, whereas current medications received by the patients were considered and patients receiving corticosteroids and/or immunosuppressant therapy for management of their disease were not excluded. Moreover, all enrolled patients were further retrospectively traced regarding their treatment regimens throughout the 3-month duration prior to their recruitment making sure that no recent alteration in the treatment protocol was applied, in order to exclude the impact of systemic drug modulation on the ocular results throughout the study period.
Full general examination and skin pathergy test were carried out for all patients, to establish the diagnosis of the disease.
Blood specimens were collected after an overnight fast, for complete blood count, liver function tests, platelets count, erythrocyte sedimentation rate, antinuclear antibody level, and renal function tests, prior to the initiation of intravitreal and/or retrobulbar therapy, as well as chest X-ray to exclude chest infection or TB.
All patients underwent complete ophthalmological examination, that is, best corrected visual acuity (BCVA) testing, anterior segment examination, slit lamp biomicroscopy, tonometry, and indirect ophthalmoscopy, whereas other investigations including fundus photography, fluorescein angiography, and OCT were performed as indicated.
Patients with other ocular pathologies, end-stage disease with no light perception attributable to retinal ischemia and/or optic atrophy, bilateral irreversible blindness, ocular hypertension, or glaucoma, as well as concurrent active infection, were excluded from the current study.
The patients were nonrandomly scheduled for intravitreal methotrexate (MTX) injection in their right eyes (
In
For retrobulbar injection, the needle was inserted at the inferotemporal aspect of the lower lid directed towards the orbital apex, and the patient was asked to look straight ahead while the globe was pushed towards the superior orbit with the index finger of the noninjecting hand; thus, a quick pass of the needle, in the absence of any eye movement, assures nonpenetration of the globe.
Patients were examined one week after injection and monthly thereafter for a period of 6 months. At each visit, measurement of the best corrected visual acuity (BCVA) and intraocular pressure (IOP) was made. Slit lamp biomicroscopy and dilated fundoscopy to view individual cells within the vitreous cavity and assessment of posterior segment were done.
Remissions were considered with <1+ cells in the anterior chamber or vitreous, whereas relapses were defined as the development of ≥1+ cells in the anterior chamber or vitreous cavity.
Data were coded and analyzed using the statistical package SPSS version 15 for Windows. Data were summarized using mean ± standard deviation (SD) for quantitative variables and frequency and percentage for qualitative variables. Significant differences were calculated using Student’s
In this cross-sectional nonrandomized comparative study, 31 adult BD male patients with a mean age of 29.7 years ± 6.17 and a mean disease duration of 5.45 years ± 2.39 who presented with nearly symmetrical bilateral posterior segment involvement were enrolled.
Anterior chamber reaction in the form of flare and cells ranging from + to ++ was documented in 20 (64.5%) eyes in
For
The preinjection BCVA ranged within 0.1–0.5 with a mean of
In eyes with preinjection anterior chamber activity (38 eyes), an improvement of anterior chamber activity was achieved in all eyes after injection throughout the scheduled follow-up visits, whereas 90% of eyes showed complete improvement within the first 2 weeks after injection, whereas no significant differences were noted regarding either group (
An improvement in vitreous activity was achieved in 47 eyes, with complete resolution in 10 eyes by the end of 1st week, 12 eyes by the end of the 2nd week, 9 eyes by the end of 1st month, and 12 eyes at 2 months after injection, whereas 4 eyes (8.5%) failed to achieve complete resolution of vitreous reaction by the end of the follow-up period, again with no differences between either group of eyes (
No postinjection elevation of IOP was detected in any of the eyes injected with intravitreal MTX (
Therefore, in
Meanwhile, in
Moreover, despite that IOP elevation, no other complications were encountered in either group of eyes during the injection procedure or throughout the follow-up period.
A nonsignificant improvement of BCVA was recorded in 24 eyes (77.4%) in MTX injected eyes, that is,
The pre- & post-injection improvement of BCVA.
| | | |||
---|---|---|---|---|---|
Pre-injection | Post-injection | Pre-injection | Post-injection | Between groups | |
Min | 0.1 | 0.2 | 0.125 | 0.3 | |
Max | 0.5 | 0.6 | 0.5 | 0.6 | ≤ |
Mean | | | | | |
| ≤ | ≤ |
A considerable improvement in ocular inflammatory reaction as well as visual acuities has been achieved in 58 eyes (93.5%) in both groups throughout the follow-up period, with no significant differences between both groups (
Behçet’s disease is a chronic noninfectious condition with ocular involvement in up to 80% of cases, which are characterized by being chronic with a remitting course, whereas the main goal of treatment is to induce and maintain a long duration remission of the disease condition [
Periocular and intravitreal drug delivery have been proposed in a trial to overcome the potential side effects of systemic drugs used as well as to insure a high concentration level of the drug delivered to the target organ for superior therapeutic effect [
In the present study, the effect of intravitreal MTX injection was compared with retrobulbar corticosteroid injection in cases with posterior segment involvement with BD, regarding the control of inflammatory manifestations as well as the induction of remission.
Reviewing literature, the efficacy of retrobulbar corticosteroids in ocular inflammatory conditions was noted to be evaluated by many investigators, with satisfactory results in chronic cases. Meanwhile, limited publications regarding the role of intravitreal MTX in intraocular inflammatory conditions and no published comparative studies regarding both modalities were retrieved [
In the present study, 31 adult male patients with established BD and bilateral posterior segment involvement were intravitreally injected with 400
In the present study, an improvement of anterior and posterior segment activity was achieved in all cases, with complete resolution of anterior segment reaction in 90% of cases during the first 2 weeks, whereas posterior segment resolution was achieved in 93.6% of eyes by the end of the 2nd month after injection.
Our results are comparable to those reported by Okada et al. [
Moreover, the observed improvement of inflammatory activity may be explained based on previous published data with documented significant improvement of anterior chamber flare and reduced protein accumulation by laser flare photometric studies following orbital floor triamcinolone acetonide injections, as well as the decreased intraocular cytokine levels after intravitreal MTX in cases with refractory inflammatory reactions [
77.4% of eyes with intravitreal MTX achieved an improvement of the mean BCVA from
Again our data are still comparable with those recorded by Bae and Lee [
Furthermore, we noted a mean improvement of BCVA from
In our study, no significant changes in the mean IOP values were noted after injection in
Moreover, 2 eyes showed a transient elevation of IOP following retrobulbar TAA injection, at a rate of 6%, which was controlled within 4–6 weeks with no significant alterations in IOP values postinjection by the end of our scheduled follow-up.
In the present work, the incidence of ocular hypertension was considered the least as compared with other published data following retrobulbar steroid injection, which may be attributed to meticulous patient selection in the present study, as cases with ocular hypertension or previous glaucoma were excluded [
Relapses that required reinjection were noted in 11 eyes after MTX injection after a mean duration of
Meanwhile, in
Furthermore, our results are not comparable with published results by Gamal et al. [
In the present study, no significant statistical differences were elicited between either treatment modalities; however, based on our clinical observations, the lower incidence of relapses as well as the longer duration of remission noted after intravitreal MTX injection may encourage this treatment modality over retrobulbar TAA injection.
Furthermore, the risk of IOP elevation after retrobulbar injection may still favor intravitreal MTX injection in ocular BD.
Despite being less invasive than the intravitreal approach, the efficacy of retrobulbar TAA injection may be questioned, being a blind procedure that may not ensure a direct concentration of the drug at the target area, for example, the macular region in cases with CME, as well as the increasing incidence of IOP elevations; however, intravitreal injection may ensure adequate delivery of the drug to the eye.
Intravitreal MTX, despite being more invasive, however, may ensure better control of inflammatory reaction and may encourage longer remission as compared to retrobulbar TAA, with decreasing risk of IOP elevation. Further studies on a larger number of patients and longer follow-ups are recommended to ensure the efficacy of intravitreal MTX in controlling posterior uveitis in BS patients.
The authors declare that they have no competing interests.