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 Table of Contents  
Year : 2013  |  Volume : 106  |  Issue : 3  |  Page : 172-179

Triple intravitreal bevacizumab, sub-Tenon's triamcinolone, and panretinal photocoagulation in Eales' disease

Ophthalmology Department, Mansoura University, Mansoura, Egypt

Date of Submission15-May-2013
Date of Acceptance14-Jul-2013
Date of Web Publication28-Feb-2014

Correspondence Address:
Abeer Khattab
Ophthalmology Department, Mansoura University, Mansoura
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2090-0686.127380

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Eales' disease (ED) is an idiopathic inflammatory vasoproliferative retinal disease primarily affecting the peripheral retina of young and apparently healthy adult men, mostly from the Indian subcontinent. It is characterized by peripheral retinal inflammation, retinal neovascularization, and recurrent vitreous hemorrhage, with or without retinal detachment.
This study was carried out to evaluate triple therapy, with intravitreal bevacizumab (IVB), posterior sub-Tenon's (SBT) triamcinolone, and panretinal photocoagulation (PRP), in ED patients with vitreous hemorrhage and its associated vasculitis, neovascularization, and macular edema.
This was a prospective, interventional case series.
Patients and methods
This study included 20 eyes of 20 patients with vitreous hemorrhage because of ED. Preoperative evaluation included patient age, sex, race, medical history, medications, complete ophthalmological examination, and diagnostic laboratory evaluation. All eyes were treated with IVB, posterior SBT triamcinolone, and PRP. The follow-up period was up to 6 months. The main outcome measures were visual acuity, intraocular pressure changes, and recurrence of vitreous hemorrhage.
A statistically significant improvement in visual acuity was observed at 1 week and 1, 3, and 6 months postoperatively. There was no statistically significant change in intraocular pressure at any of the postoperative follow-up intervals. There was no intraoperative or postoperative complication. None of the patients included had any recurrence during the follow-up.
The triple therapy with IVB, posterior SBT triamcinolone, and PRP seems to be effective in the treatment of ED patients with dense vitreous hemorrhage and its associated vasculitis, neovascularization, and macular edema.

Keywords: Bevacizumab, Eales′ disease, intravitreal, panretinal photocoagulation, sub-Tenon′s, triamcinolone

How to cite this article:
Khattab A, Turkey M. Triple intravitreal bevacizumab, sub-Tenon's triamcinolone, and panretinal photocoagulation in Eales' disease. J Egypt Ophthalmol Soc 2013;106:172-9

How to cite this URL:
Khattab A, Turkey M. Triple intravitreal bevacizumab, sub-Tenon's triamcinolone, and panretinal photocoagulation in Eales' disease. J Egypt Ophthalmol Soc [serial online] 2013 [cited 2023 Feb 1];106:172-9. Available from: http://www.jeos.eg.net/text.asp?2013/106/3/172/127380

  Introduction Top

Eales' disease (ED), first described by the British ophthalmologist Henry Eales in 1882, is an idiopathic inflammatory vasoproliferative retinal disease primarily affecting the peripheral retina of young and apparently healthy adult men mostly from the Indian Subcontinent descent between 20 and 40 years of age [1],[2],[3]. It is a clinical condition characterized by the sequential cascade of peripheral retinal inflammation (i.e. perivasculitis, the peripheral sheathing of veins leading to sclerosis of the retinal vessels, ischemia of the retina, and, hence, retinal nonperfusion), culminating in retinal neovascularization and recurrent vitreous hemorrhage, with or without retinal detachment [3],[4].

The etiopathogenesis of this disease is still debatable. Since its original description, many investigators have considered an association with tuberculosis (or hypersensitivity to tuberculoprotein) to be the prime cause of this disease [5],[6],[7]. A T-cell-mediated immune mechanism may play a key role in retinal vasculitis (the inflammatory stage) in this disease. There is extensive retinal ischemia [resulting in the release of angiogenic factors such as vascular endothelial growth factor-6 (VEGF-6)] subsequent to postphlebitic occlusive vasculopathy [1]. Recent immunological, molecular biological, and biochemical studies indicate a probable multifactorial etiology [8],[9]. Human leukocyte antigen, retinal autoimmunity, mycobacterial tuberculosis genome, and free radical-mediated damage play a role in the etiopathogenesis of this disease [10].

Although its etiopathogenesis remains unclear, the management options are quite well established. The management depends on the stage of the disease. Systemic or periocular corticosteroids had been found to be beneficial in the active perivasculitis stage [3],[11]. Panretinal photocoagulation (PRP) is indicated in patients with gross capillary nonperfusion or retinal neovascularization. Photocoagulation remains the mainstay of therapy in the proliferative stage of ED [5],[10],[11]. Recently, intravitreal bevacizumab (IVB) has been explored as a possible therapeutic modality in the management of early stages of ED [12],[13]. The results of vitrectomy in nonresolving vitreous hemorrhage with or without retinal detachment are satisfactory [2],[4],[5],[14].

  Objective Top

The aim of this study was to evaluate triple therapy with IVB, posterior sub-Tenon's (SBT) triamcinolone, and PRP in ED patients with dense vitreous hemorrhage and its associated vasculitis, neovascularization, and macular edema.

  Patients and methods Top

This study was a prospective, interventional case series that included 20 eyes of 20 patients who were recruited from the ophthalmology outpatient clinic of Al Bahar Eye Center, Ibn Sinai Hospital of Kuwait Ministry of Health, during the period from August 2010 to December 2010. The clinical diagnosis of ED was made on the basis that all patients presented with sudden painless loss of vision in one eye because of varying degrees of vitreous hemorrhage, which was associated with neovascularization, perivasculitis, and, occasionally, cystoid macular edema, discovered concurrently with the rapid clearance of media. All the fellow eyes showed variable degrees of asymptomatic signs starting from perivasculitis and neovascularization to the degree of small preretinal hemorrhages, macular edema, and minimal vitreous hemorrhage. Patients were excluded if they had a history of diabetes, hypertension, sarcoidosis, collagen vascular disorder, blood dyscrasias, hemoglobinopathies, high myopia, ocular trauma, previous surgery, corneal or lenticular pathology, or advanced disease process in both eyes as vitreous traction bands and retinal detachment.

Demographic, medical, and ophthalmic data were recorded in detail. Demographic information included age, sex, race, place of residence, occupation, travel, or treatment history. Ophthalmic evaluation included the determination of best-corrected visual acuity (BCVA) using Snellen's chart, anterior segment evaluation using slit-lamp biomicroscopy, and intraocular pressure (IOP) measurement using applanation tonometry. The diagnosis was made using an indirect ophthalmoscope, slit-lamp biomicroscopy with a 78 D noncontact lens, and fluorescein angiography after clearance of vitreous hemorrhage. Ultrasonography was performed to exclude the presence of tractional retinal detachment.

Several tests were carried out in all patients to rule out mimicking diseases and to ensure that the patients fulfilled the inclusion criteria. These included complete blood count, erythrocyte sedimentation rate, blood sugar, protein electrophoresis, blood chemistry, chest radiograph, urine analysis, C-reactive protein, sickle cell disease screening test, VDRL, FTA-ABS,  Brucella More Details titer, antinuclear antibody, and antineutrophil cytoplasmic antibody.

Informed consent was obtained from each patient after explaining the nature of the disease and surgical details as well as the off-label use of IVB. The study was approved by the Institutional Review Board of Al Bahar Eye Center.

An IVB injection was administered in the operating room under full sterile precautions. Under topical anesthesia, using topical benoxinate hydrochloride 0.4%, after thorough cleaning and preparation with topical 5% povidone-iodine (Betadine Alcon Laboratories Inc., Fort Worth, Texas, USA), an IVB injection of 1.25 mg in 0.05 ml of Avastin (Roche) was administered 4.0 mm posterior to the limbus using a 27-G needle transconjunctivally through the temporal inferior pars plana. The tip of the needle was visualized in the mid-vitreous and the drug exits the needle tip in the form of a gel into the vitreous cavity on injection. The needle was withdrawn and the site was compressed with a sterile tip of a cotton bud for 4-5 s. The second step, for the posterior SBT injection, 1 ml of 40 mg/ml of triamcinolone acetonide (TA, Kenacort 40; Bristol-Myers Squibb Pharmaceuticals) was administered in the inferotemporal quadrant using a 27-G needle on a 2.5-ml syringe. The patients were directed to look into the extreme superonasal field of gaze. The conjunctiva and the Tenon's capsule were penetrated with the bevel of the needle toward the globe. The needle was advanced toward the macular area, taking care to remain in contact with the globe until the hub was firmly pressed against the conjunctival fornix and then the corticosteroid was injected slowly. Moxifloxacin (Vigamox) eye drops were prescribed and continued for a week.

PRP was started as soon as any part of the media was cleared. This ranged from the second day up to the third week after presentation with an average of 9.9 days. PRP was completed within three to four sessions with a gap of at least 1 week in between. Also, PRP was carried out in all fellow eyes that had any of the asymptomatic signs including perivasculitis, neovascularization, small preretinal hemorrhages, and minimal vitreous hemorrhage. The details of laser therapy were as follows:

  1. Total number of burns, 2000-3500.
  2. Intensity of burns, 350-500 mW.
  3. Size of burn, 300-500 μm.
  4. Exposure time, 0.1 s.

The follow-up period continued for 6 months. Patients were seen on the first postoperative week and at 1, 3, and 6 months postoperatively. During each follow-up visit, the following were performed: BCVA assessment using Snellen's chart, applanation tonometry, and fundus examination. Fluorescein angiography was carried out once the media became clear. Any persistence or recurrence of vitreous hemorrhage, vasculitis, neovascularization, or macular edema was recorded.

Statistical analysis was carried out using the SPSS statistics software package version 17.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Normality of the data analyzed was confirmed by the Kolmogorov-Smirnov test. For parametric analysis, the Student t-test for paired data was used for comparison between preoperative and postoperative data. However, when nonparametric tests were needed, the Wilcoxon rank-sum test was applied. Differences were considered statistically significant when the associated P-value was less than 0.05.

  Results Top

This study included 20 eyes of 20 patients. Nineteen (95%) of our patients were men and one (5%) was female woman. The age of our patients ranged between 19 and 34 years, with a mean ± SD of 25 ± 4.17 years. Race distribution was as follows: 11 Indians, four Bangladeshi, three Pakistani, one Sinhalese, and one Nepali; all patients were from the Indian subcontinent. All patients had bilateral involvement.

Fluorescein angiography delineated the regional vascular abnormalities. These included leakage of dye because of breakdown of the inner blood-retinal barrier, staining of the blood vessel wall with fluorescein, capillary nonperfusion, capillary dilatation, arteriovenular shunts, and fluorescein extravasations through the pathological neovascularization.

The mean baseline BCVA at 1 week and at 1, 3, and 6 months after injection are shown in [Table 1]. After the triple procedure, the eyes showed significant improvement in BCVA at all postinjection follow-up intervals when compared with the baseline values and this improvement was statistically highly significant where the P-value was 0.00.
Table 1: Best-corrected visual acuity (logMAR)

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The mean baseline IOP at 1 week and at 1, 3, and 6 months after injection are shown in [Table 2]. The eyes showed no significant increase in the IOP at any of the postinjection follow-up periods when compared with the baseline values. Only two eyes showed an increase in IOP on the first postoperative week and was controlled with topical b-blockers and returned to the normal range within 2 weeks.
Table 2: Intraocular pressure changes (mmHg)

Click here to view

Neither recurrence nor persistence of vitreous hemorrhage, vasculitis, neovascularization, or macular edema was detected within the 6-month follow-up period. Also, progression to tractional retinal detachment was not observed in any of the patients in this study. No serious systemic or ocular side effects such as hyphema, lens injury, glaucoma, cataract, iatrogenic retinal breaks, retinal detachment, and endophthalmitis were recorded.

  Discussion Top

Currently, ED is considered to be an idiopathic inflammatory venous occlusion that primarily affects the peripheral retina. Retinal changes include perivasculitis, mainly periphlebitis, and peripheral nonperfusion [15]. This inflammation-induced vascular occlusion can lead to a proliferative vascular retinopathy with sequelae such as recurrent vitreous hemorrhage and tractional retinal detachment [16],[17],[18].

Different lines of management were reported in ED depending on the stage. These included systemic, intravitreal, and periocular steroids, PRP, and retinal surgery. A particular patient may require one or more of the above modalities of treatment, as quite frequently the fellow eye has a different stage of the disease. Often, multiple or repeated treatments fail to control the disease or its recurrence. To our knowledge, this is the first report of the use of this triple procedure (IVB injection, posterior SBT injection of TA, and PRP) for the management of vitreous hemorrhage and its associated vasculitis and macular edema in ED. The aim of this combination was to aid rapid clearance of vitreous hemorrhage and neovascularization and decrease the recurrence rate with the use of an IVB injection in addition to curing the vasculitis and macular edema, if present, and also decreasing the recurrence rate through the use of a posterior SBT injection of triamcinolone; finally, PRP was used to stabilize the condition.

The use of steroids should be beneficial in patients with tuberculin hypersensitivity and retinal periphlebitis. Rosen et al. [19] reported seven patients with retinal vasculitis in the presence of a strongly positive Mantoux test. The characteristic features were a moderate vitreous infiltrate, severe periphlebitis, and a marked tendency to peripheral retinal capillary closure leading to new vessel formation. The patients were treated with systemic corticosteroids, with or without antituberculous therapy. All cases of retinal vasculitis were resolved with treatment. Reactivation of miliary tuberculosis with choroidal tubercles occurred in one patient treated with corticosteroids alone [19]. Therefore, the use of systemic steroids with an appropriate antituberculous therapy, even in the absence of active systemic disease, was strongly suggested to avoid reactivation of the systemic illness [16]. The efficacy of systemic or periocular corticosteroids in the inflammatory stage of ED was studied in another nonrandomized clinical trial where systemic steroid (1 mg/kg of body weight) and posterior SBT injection of steroid (TA 40 mg/ml) were found to be beneficial if there was involvement of three quadrants with cystoid macular edema. Systemic corticosteroids alone were helpful when there two quadrants were involved. In the case of one quadrant involvement, periocular corticosteroids were administered. However, the natural course of ED remained unaltered despite steroid therapy [10].

To reduce the side effects and the cost of management, Ishaq et al. [20] studied the effects of intravitreal triamcinolone acetonide (IVTA) in patients with ED. Fluorescein fundus angiograms of 12 eyes of 12 ED patients were taken before enrollment. These patients received 0.1 ml of 40 mg/ml (4 mg) IVTA through pars plana under topical anesthesia. Fluorescein fundus angiography was again performed in the eighth week to monitor response toward treatment. A decrease in areas of late perivascular dye extravasations on fluorescein angiography was used as a marker for improvement. Ten of a total of 12 (83.33%) eyes treated with IVTA showed a significant reduction of late leakage from retinal vessels on fluorescein fundus angiography. Two of 12 eyes (16.67%) did not show a considerable decrease in late perivascular fluorescein dye leakage after 8 weeks of IVTA when compared with an IVTA injection. Two patients (16.67%) showed a significant increase in IOP after IVTA. They concluded that intravitreal steroids may be advocated for the management of idiopathic retinal vasculitis with avoidance of systemic steroid complications, and may minimize the need for more invasive procedures [20].

In this study, a significant improvement was found in visual acuity without any significant change in IOP up to the end of the follow-up period. This was in agreement with several studies that reported equal efficacy of the posterior SBT approach with lower incidence of elevation in IOP as well as less induction of cataract. To decrease the side effects of IVTA, in this study, it was preferred to administer steroids through the posterior SBT approach as these patients were young in their accommodative period. Cellini et al. [21] assessed the efficacy of the IVTA injection as compared with posterior SBT injection for the treatment of cystoid diabetic macular edema. In the same patients, one eye was assigned to 4 mg of IVTA injection and the fellow eye was then treated with 40 mg SBT injection of TA. The visual acuity was measured before treatment and 1, 3, and 6 months after treatment with the ETDRS chart as was the thickness of the macula with optical coherence tomography and IOP. All eyes treated with both IVTA and SBT injections showed significant improvement in visual acuity up to the third month after treatment. Central macular thickness was significantly reduced in all eyes treated with an IVTA injection and in those treated with an SBT injection up to the third month after treatment. The difference between the eyes treated with the IVTA injection and those treated with an SBT injection became significant 6 months after treatment. IOP of the eyes treated with an IVTA injection increased significantly after 1, 3, and 6 months when compared with the baseline value. The SBT injection eyes did not show any significant increase in IOP at any of the post-treatment follow-up periods when compared with the baseline value. They concluded that the parabulbar SBT approach can be considered a valid alternative to an intravitreal injection. In another study by Choi et al. [22], both intravitreal and posterior SBT injections of TA resulted in significant improvements in visual acuity at 1 month and 3 months after injection. Both groups showed a significant decrease in central macular thickness at 1 month and 3 months after injection. IOP in the intravitreal injection group was significantly higher than that in the posterior SBT injection group at 3 months after injection.

In this study, we encountered no intraoperative or postoperative complications of the SBT approach apart from the two eyes with a temporary elevation in IOP in the first postoperative week, which was controlled with b-blockers and reverted to the normal range after 2 weeks. The SBT approach is clearly less invasive than the intravitreal one, although this commonly used method is not free from potential complications such as the accidental injection directly into the choroidal or retinal circulation, perforation of the ocular bulb, occlusion of the central retinal artery, and cataract. Other complications described are blepharoptosis, orbital fat atrophy, strabismus, and conjunctival necrosis. IOP does not increase as sequelae of this approach, with the exception of that in steroid responder patients [21].

Thanks to its effect on visual acuity and macular thickness, posterior SBT injection of TA was chosen to be combined with laser photocoagulation to improve the results. PRP could be started in those patients beginning from the second day up to the third week after presentation with an average of 9.9 days. We assume that this combination of IVB and posterior SBT triamcinolone enabled us to start laser photocoagulation earlier, with better results. This was in agreement with a study carried out by Shimura et al. [23]; they prospectively evaluated the efficacy of an SBT injection of TA before grid pattern laser photocoagulation (G-PC) for the treatment of diffuse diabetic macular edema in 42 eyes of 37 consecutive patients. After the TA injection, foveal thickness and visual acuity improved, and subsequent G-PC maintained the improvement for up to 24 weeks without recurrence of diffuse diabetic macular edema. In contrast, G-PC without the TA injection induced transient worsening of foveal thickness and visual acuity, and then both gradually improved. The laser intensity required in TA-injected eyes was less than that for the control. They found that SBT injection of TA before G-PC enables treatment with a lower intensity of laser spots and also prevents the decrease in central visual field sensitivity, all of which have clinical advantages for G-PC. In a recent study, Shen et al. [24] characterized the pharmacokinetics of TA in aqueous, vitreous, and systemic circulation in 36 patients (36 eyes) who received a single posterior SBT injection of TA (40 mg in 0.4 ml). Aqueous, vitreous, and blood samples were obtained at 1-h, and at 1-day, 3-day, 5-day, 10-day, 14-day, 21-day, and 28-day time points after the posterior SBT TA injection. The TA concentration in the samples was measured, and pharmacokinetic parameters were calculated. They concluded that posterior SBT TA application can provide a sustained high local ocular TA level while also resulting in a very low systemic TA level, which may be well below the normal glucocorticoid level in humans.

PRP was used for the treatment of neovascularization with good results in 1954 and since then, it has become the treatment of choice for patients with neovascularization [25]. The aim of photocoagulation in ED is to regulate the circulation by diverting blood from hypoxic areas to a healthy retina, thereby decreasing the formation of vasoproliferative factors, to obliterate surface neovascularization, and to close leaking intraretinal microvascular abnormalities [10]. Historically, xenon arc photocoagulation was first used for ED; subsequently, others had reported the efficacy of photocoagulation in the proliferative stage of ED. Combined xenon arc photocoagulation in the paracentral zone and anterior retinal cryopexy in the periphery had been used successfully. Currently, laser photocoagulation is mostly used because of the obvious advantage of reaching the retinal periphery, where retinal ischemia and neovascularization are mostly observed. Although argon green laser is most commonly used, in case of significant cataract or mild vitreous hemorrhage, red krypton laser can be used effectively. Such a laser can now be delivered either through a slit-lamp delivery system or an indirect ophthalmoscope [10].

Magargal et al. (26) have reported the efficacy of PRP in controlling the neovascularization and achieving complete regression of ED. In another series, complete regression of vasoproliferative disease was achieved after extensive full PRP in 21 eyes that showed new vessel formation and peripheral capillary closure with or without vitreous hemorrhage. Therefore, they strongly recommended immediate laser photocoagulation to rapidly achieve a full and extensive PRP before vitreous hemorrhage; also, fibrovascular proliferation and traction can develop [16].

Between 1970 and 1991, Atmaca et al. [27] examined 466 cases with ED. In all, 359 eyes of these 466 cases received photocoagulation treatment. The mean age of the patients was 30.4, ranging between 14 and 55 years. Ten eyes with persistent vitreous hemorrhage were subjected to pars plana vitrectomy before photocoagulation. A total of 210 eyes were treated with xenon arc, 135 with argon laser, 12 with krypton laser, and two with yellow dye laser. Hypoxic areas and retinal neovascularizations were closed completely in 298 eyes. In 21 eyes with elevated neovascularizations intruding into the vitreous cavity feeder vessel, photocoagulation was carried out. Twenty-four eyes with disc neovascularization were treated with PRP. Twelve eyes with branch vein occlusion and four eyes with central vein occlusion received photocoagulation treatment in areas of nonperfusion and retinal neovascularization. At a mean follow-up of 43 months, seven new retinal neovascularizations and three new disc neovascularizations developed in eyes that had previously received photocoagulation for retinal neovascularization and hypoxia. Nine of 21 eyes with elevated neovascularizations developed vitreous hemorrhage. Disc neovascularization resolved completely in 13 of 24 eyes; it regressed partially in eight eyes and did not respond to treatment in three eyes. The visual acuities improved in 12.3%, were maintained in 77.4%, and deteriorated in 10.3% of the eyes after treatment. They concluded that periodic follow-up and early photocoagulation treatment is useful in stabilization of the retinal lesions and in maintenance of functional levels of vision in ED.

Although laser photocoagulation should be the first line of treatment in ED, it cannot always induce regression of retinal neovascularization. In such cases, vitrectomy may further enhance therapeutic success. Dehghan et al. (28) determined visual outcomes and regression of retinal neovascularization following laser photocoagulation and/or vitrectomy in eyes with ED. In a retrospective noncomparative study, the authors reviewed the existing data of 67 eyes of 54 patients with a diagnosis of ED who had undergone laser photocoagulation and/or vitrectomy on the basis of their clinical presentations. Their results showed that both laser therapy and vitrectomy improved visual acuity and induced regression of retinal neovascularization. Forty-three eyes were subjected to laser therapy; their rate of visual acuity improved from 53% before treatment to 60% after treatment. Twenty-four eyes were subjected to vitrectomy; the rate of visual acuity improved from 13% before surgery to 38% after surgery. In eyes that were subjected to laser therapy, additional laser therapy controlled recurrent neovascularization in 47% of the eyes, but ultimately, 12% of them required vitrectomy. In the primary vitrectomized group, additional required treatments were repeated vitrectomy in 21% and/or laser therapy in 29% of the eyes.

The pathogenesis of ED remains largely unknown. There is a huge controversy on the underlying mechanism responsible for the initiation and occurrence of ED. However, the disease ultimately progresses to a florid presentation mimicking any other vasoproliferative disorder where endothelial dysfunction plays a key role. Endothelial dysfunction, a concomitant of endothelial cell activation, is characterized by the expression of leukocyte adhesion molecules, vascular permeability, and, most importantly, angiogenesis. The finding that inflammation is often associated with increased angiogenesis can be explained by inflammation-induced production of angiogenic factors, either from vascular or other tissue cells or from infiltrating leukocytes [29]. Tumor necrosis factor-a, a major inflammatory cytokine, acts as an angiogenic stimulator in inflammation-mediated pathologic angiogenesis. Although there are some variations in opinions on the angiogenic properties of tumor necrosis factor-a, it has been proposed that it may induce angiogenesis through various secondary angiogenic factors such as platelet-derived growth factor, VEGF, interleukin-8, and basic fibroblast growth factor [1].

Bevacizumab (Avastin; Genentech, South San Francisco, California, USA) is a monoclonal antibody that binds all isomers of VEGF [30] IVB had been used in treating inflammatory ocular neovascularization and led in the long term to significant mean visual improvement of 2.2 lines and significant foveal flattening in a wide variety of inflammatory ocular diseases without major complications [31].

An IVB injection was used in this procedure to aid regression of retinal neovascularization and resolution of vitreous hemorrhage in addition to alleviating the need for vitreoretinal surgery. It was also aimed at reducing the recurrence rate of this disease, which was reported previously after the use of laser photocoagulation alone or even after vitrectomy. In this study, there was rapid clearance of vitreous hemorrhage, regression of retinal neovascularization, and absence of recurrence after 6 month of follow-up. These results are in agreement with those reported by other authors who evaluated the use of IVB in ED. Küçükerdönmez et al. [32] reported a case of presumed ED that showed regression of retinal neovascularization after the use of IVB. Broad retinal neovascularization in this patient with presumed ED did not regress despite adequate photocoagulation treatment, and bevacizumab (1.25 mg) was injected intravitreally. The patient was followed up for 1 year. One week after injection, fluorescein angiography showed marked regression of retinal neovascularization. After 12 months, visual acuity had improved and no signs of recurrence were observed. They concluded that IVB may be effective as an adjunctive treatment of retinal neovascularization in patients with ED.

In a retrospective, interventional case series study, two patients with proliferative ED were managed with an IVB injection of 1.25 mg. The presence of persistent retinal neovascularization despite adequate laser photocoagulation led to recurrent episodes of vitreous hemorrhage in the first patient. The second patient had florid retinal and disc neovascularization with a dispersed vitreous bleed, which prevented laser therapy. Both patients were followed up for 6 months. Rapid regression of the retinal neovascularization and clearing of the vitreous hemorrhage were observed in both cases following IVB therapy, thus allowing laser photocoagulation. In both patients, the visual acuity improved, and no signs of recurrence were observed 6 months after treatment. It was concluded that IVB injections may be effective as an adjunctive or an alternative treatment of retinal neovascularization in ED, where inadequate visualization precludes laser photocoagulation. This approach may also be useful in avoiding vitreoretinal surgical intervention in certain cases. IVB was well tolerated by the patients and no adverse effects were observed [33].

There was another case report of a 23-year-old man with a history of recurrent uncontrolled vitreous hemorrhage in both eyes who underwent vitrectomy and laser photocoagulation in both eyes and presented with sudden diminution of vision in the right eye. On examination, his BCVA was 20/2000 and 20/30 in the right and the left eye, respectively. Indirect ophthalmoscope showed fresh vitreous hemorrhage with no fundus view in the right eye; B scan ultrasonography of the right eye was suggestive of the same with no evidence of retinal detachment. The patient's right eye was injected with 0.05 ml (1.25 mg) of IVB. At the 1-month follow-up, his vision had recovered to 20/30 in the right eye. A fundus fluorescein angiogram did not show any evidence of neovascularization. At the 3-month and 1-year follow-up, there was no recurrence of neovascularization and vision was stable in both eyes. Thus, the use of IVB in the management of recurrent vitreous hemorrhage in ED was highlighted [34].

The use of IVB as an adjunctive treatment in two cases of advanced ED with vitreous hemorrhage and tractional retinal detachment before vitreoretinal surgery was also reported [12]. In two patients presenting with vitreous hemorrhage, retinal neovascularization, and localized tractional retinal detachment, 1.25 mg of IVB was injected before vitrectomy, membrane peeling, and endolaser photocoagulation of the retina. Regression of the retinal neovascularization with resolution of dye leakage on fluorescein angiography was observed in both cases. Membrane peeling could be performed with minimal bleeding during vitreoretinal surgery in both cases. They concluded that bevacizumab may be a possible adjunctive treatment to vitreoretinal surgery for the management of ED with tractional retinal detachment [12].

Another advantage of this triple procedure is to avoid the complications of repeated IVB injection. However, Patwardhan et al. [35] investigated the role of IVB in ED with dense vitreous hemorrhage in a prospective randomized control trial. Twenty eyes of 20 patients with dense vitreous hemorrhage because of ED were distributed randomly in group 1 (n = 10) and group 2 (n = 10). The eyes in group 1 received an IVB injection (1.25 mg/0.05 ml) every 4 weeks and the eyes in group 2 were observed. Patients of both groups were followed up every 2 weeks. Vitrectomy was performed in case of nonresolving vitreous hemorrhage of grade 2 or more after 3 months of enrollment or immediately if retinal detachment was detected. Intraoperative difficulties while performing surgery and excessive bleeding were noted. The primary outcome measures were reduction in the grade of vitreous hemorrhage and the need for vitrectomy. Only one eye from group 1 and two eyes from group 2 showed a decrease in vitreous hemorrhage of grade 2. However, all three eyes required vitrectomy because of persisting poor vision. Postoperative mean vision ± SD in group 1 was 1.2 ± 0.57 in logarithm of the minimum angle of resolution units, and in group 2, it was 0.78 ± 0.41 in logarithm of the minimum angle of resolution units (P = 0.086, 95% confidence interval). Three eyes (30%) in group 1 had tractional retinal detachment after a single IVB injection, whereas none of the group 2 eyes had tractional retinal detachment. Vitrectomy was performed in all three eyes and had a poor visual outcome after surgery. No intraoperative difficulties were noted in either group. Their study showed that repeated IVB in patients with ED with dense vitreous hemorrhage may not hasten the resolution of vitreous hemorrhage or reduce the need for vitrectomy. Moreover, tractional retinal detachment may be a serious complication of therapy and should hence be monitored closely because it entails a poor visual prognosis.

Apart from its apparent efficacy, IVB also appears to be relatively safe in the short term, with no cases of ocular toxicity, retinal detachment, raised IOP, or thromboembolic events being reported in any of the literature reviewed [30]. This is in agreement with our study, where there were no complications of this procedure. However, two cases of acute endophthalmitis occurred 2 days after IVB and coagulase-negative staphylococci were isolated from vitreous specimens in both cases while two potentially drug-related adverse events (ischemic stroke and myocardial infarction) were previously reported [30].

  Conclusion Top

This study may suggest new avenues in the treatment of ED. To our knowledge, it is the first time that this triple procedure has been used to treat vitreous hemorrhage in ED. IVB injection aided the rapid disappearance of vitreous hemorrhage and neovascularization and also helped in decreasing the recurrence rate. Posterior SBT injection helped in curing vasculitis and macular edema, if present, and also in decreasing the recurrence rate. PRP stabilized the condition until the end of the follow-up period, with no recurrence. We encountered no complications of the triple technique used in this study; however, further studies are needed with larger samples and a longer follow-up period to prove the efficacy and safety of this technique.

  Acknowledgements Top

Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Table 1], [Table 2]


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