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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 17  |  Issue : 2  |  Page : 132-138

Focal laser application versus bevacizumab for treatment of central serous chorioretinopathy


Faculty of Medicine Department of Ophthalmology, Al-Azhar University, Damietta, Egypt

Date of Submission06-Jul-2018
Date of Decision08-Aug-2018
Date of Acceptance02-Jun-2019
Date of Web Publication23-Oct-2019

Correspondence Address:
Ali A Ghali
2nd District, 2nd Block, Eng. Hassaballah Alkafrawy Street, New Damietta, 34518
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_66_18

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  Abstract 


Aim To report and compare the efficacy of macular grid laser versus intravitreal bevacizumab injection (IVBI) in patients with central serous chorioretinopathy (CSCR).
Patients and methods A prospective study on 36 eyes of 35 patients with CSCR was conducted. The diagnosis of CSCR was established by fluorescein angiography and optical coherence tomography (OCT). All patients underwent measurement of best-corrected visual acuity, intraocular pressure, dilated fundus examination, and (OCT) imaging at baseline and follow-up visits. Fluorescein angiography was performed at baseline visit and thereafter depending on clinical and OCT findings. Patients were classified into group A, comprising 19 patients who were treated with macular grid laser and group B, comprising 17 patients who were treated with IVBI. The outcome measures were the resolution of neurosensory detachment, improvement in visual acuity, and resolution of leakage. All cases were evaluated after 3, 6, 12, and 24 weeks. Data were classified into two groups and statistically analyzed.
Results In group A, the mean age of patients was 43.6 years (range, 23–52 years), there were 11 (57.89%) males and eight (42.10%) females, and the mean of follow-up period was 9.2 months (range, 7–18 months). The mean log MAR visual acuity score improved from 0.8 to 0.40 after 3 months of follow-up. The mean baseline central macular thickness (CMT) was 466 µm (range, 358–576 µm), which decreased to 309 µm (range, 268–356 µm) after 6 weeks, with statistically significance difference change from the baseline, and to 247 µm (range, 225–319 µm) after 3 months, with statistically significance difference change from the baseline (P<0.001). In group B, the mean age of patients was 39.7 years (range, 42–57 years), there were nine (52.94%) males and eight (47.05%) females, and the mean follow-up period was 9.1 months (range, 6–16 months). The mean log MAR visual acuity improved from 1.00 to 0.40 after 3 months of follow-up. The mean baseline CMT was 454 µm (range, 334–567 µm), which decreased to 312 µm (range, 264–359 µm) after 6 weeks, with statistically significant difference change from baseline, and to 252 µm (range, 232–338 µm) after 3 months, with statistically significant difference change from the baseline (P<0.001). After 3 months of follow-up time, there was no significant difference in mean CMT between booth groups (247 vs. 252 µm). The mean baseline visual acuity improved in both groups, without significant difference between them. No serious adverse effects have been observed in both groups.
Conclusion Both macular grid laser and IVBI for CSCR can lead to improvements of visual acuity and hasten recovery period. Macular grid laser may be considered as effective as anti-vascular endothelial growth factor for treatment of CSCR. More studies using larger scales may be needed to clarify the uncertain relationship between pathogenesis and results of treatment.

Keywords: bevacizmab, csr, laser


How to cite this article:
Ghali AA. Focal laser application versus bevacizumab for treatment of central serous chorioretinopathy. Al-Azhar Assiut Med J 2019;17:132-8

How to cite this URL:
Ghali AA. Focal laser application versus bevacizumab for treatment of central serous chorioretinopathy. Al-Azhar Assiut Med J [serial online] 2019 [cited 2019 Nov 22];17:132-8. Available from: http://www.azmj.eg.net/text.asp?2019/17/2/132/269764




  Introduction Top


Central serous chorioretinopathy (CSCR) is an uncommon retinopathy that occurs owing to idiopathic leakage of fluid at the level of retinal pigment epithelium (RPE), resulting in the development of well-circumscribed serous neurosensory retinal detachment often in association with serous (RPE) detachment at the posterior pole [1]. CSCR usually affects young and middle-aged male patient, especially those with type-A personality, systemic hypertension, corticosteroid therapy, and obstructive sleep apnea. Presentation is variable, but common visual symptoms include relative central scotoma, metamorphopsia, dyschromatopsia, and micropsia. Although the patient frequently manifests symptoms in one eye, but up to 18% of cases may have bilateral affection. Clinical studies suggest that CSCR is more diffuse and bilateral; even the presentation and clinical manifestations are detected only in one eye [2],[3].

The pathogenesis of CSCR is not completely understood, but a number of hypotheses have been proposed. The most accepted theory is dysfunction of the RPE with underlying choroidal circulation abnormalities resulting in exudation of fluid in the subretinal space [4],[5]. Other studies using enhanced depth imaging [optical coherence tomography (OCT)] also showed that the choroid is very thick in patients with CSCR which might indicate increased hydrostatic pressure in the choroid [6],[7].

There is no standard treatment for CSCR because of benign nature of the condition with expected good visual prognosis. The patient usually regains final visual acuity equal to visual acuity before the disease. However, spontaneous resolution of subretinal fluids (SRFs) is the typical natural history of CSCR, but 20% of patients may develop chronic CSCR with irreversible visual morbidity owing to persistent RPE and photoreceptor degeneration. Persistent SRF for 3 months or more is defined as chronic CSCR [8],[9]. Mixed results have been obtained with varying success from several studies on different lines of treatment modalities for CSCR such as focal laser photocoagulation, micropulse diode laser, photodynamic therapy with verteporfin, or intravitreal anti-vascular endothelial growth factor (VEGF) injections. Some studies suggested the use of systemic medications carbonic anhydrase inhibitors (Acetazolamide), adrenergic receptor antagonists (metoprolol and propranolol), aspirin, and steroid hormone antagonists (ketoconazole, mifepristone, finasteride, and eplerenone) [10],[11],[12],[13],[14],[15].

Some studies supporting that there are potential benefits of early effective treatment, including shortening of the symptom duration, improvement of visual outcome and decrease in the recurrence rate and chronicity, may be owing to preventing RPE damage and photoreceptor degeneration in treated eyes [4],[16],[17],[18],[19],[20].

VEGF is well known as a major mediator of vascular hyper-permeability by uncoupling endothelial cell-to-cell junction. Anti-VEGF has an effective role in decreasing the choroidal hyper-permeability without significant adverse effects or serious complications [21],[22],[23].

Thermal laser photocoagulation to the site of fluorescein leakage has been reported to hasten the recovery period of CSCR, but its use is restricted owing to its complications such as central scotomas and increased risk of choroidal neovascularization [24].


  Patients and methods Top


This is a prospective study of 36 eyes of 35 patients presented with CSCR, where 28 eyes had acute CSCR, three eyes had recurrent CSCR (more than one episode), and five eyes had chronic CSCR. The study follows the instructions of ethical committee of Al-Azhar university. In this study, the data of patients who were diagnosed with CSCR between June 2009 and July 2016 were reviewed. After obtaining informed consent, all patients underwent a complete ocular examination, including the best-corrected visual acuity (BCVA), intraocular pressure measurement, and fundus examination. The diagnosis of CSCR was established by the presence of serous macular detachment on dilated fundus examination, a typical fluorescein leakage pattern on (fluorescein angiography), and SRF accumulation evident on OCT. Patients were excluded if other conditions that could compromise visual acuity were present. All participants included in this study were followed for at least 6 months. Outcome measures were the resolution of neurosensory detachment, improvement in visual acuity, and resolution of leakage. Data were classified into two groups and statistically analyzed.

Group A included 19 eyes that were treated with macular grid argon laser.

The rationale of this procedure

  1. It has been reported that laser photocoagulation to the site of fluorescein leakage can hasten the recovery period of CSCR but is associated with serious complications.
  2. Improvement of BCVA and central macular thickness (CMT) after empirical treatment of many cases of CSCR using macular grid laser led to this comparative study.
  3. Diabetic macular edema can be improved after macular grid laser.


All cases underwent macular grid (532 argon) laser under topical anesthesia eye drops (0.4% benoxinate hydrochloride), using macular laser contact lens, with the following parameters: spot size 100 µm, the power that produced just-visible burn varied between 220 and 350 mW, and 200 ms exposure time. Using repeated mode, 30–50 shots were applied. Combined tobramycin and dexamethasone eye drops were used four times daily for 5 days. All cases were evaluated after 3, 6, and 12 weeks.

Group B included 17 eyes that were treated with intravitreal bevacizumab injection (IVBI) (Avastin; Genentech, Inc., San Francisco, California, USA).

All the injections were performed in an operating room with complete aseptic condition. Topical 0.4% benoxinate hydrochloride was applied to the ocular surface followed by scrubbing of the eye lids and lashes with 10% of povidone iodine, but conjunctiva was instilled with 5% povidone iodine. A speculum was used to stabilize the eyelid. Intravitreous injection of off-label bevacizumab was performed by a 27-G needle 3.5–4 mm from the limbus, at a dose of 2.5 mg (0.1 ml). Paracentesis was performed in some cases according to intraocular pressure. After injection, a sterile cotton swab was placed at the site of injection to prevent reflux of vitreous or drug. After the injection, the patients were instructed to apply combined tobramycin and dexamethasone eye drops to the injected eye four times a day for 5 days. Follow-up evaluations were scheduled for next day, 1 week, and then monthly till the end of follow-up. Postoperative follow-up included repeated clinical examinations and OCT to all of the patients. A repeated injection (up to three times) of bevacizumab was performed for only persistent or recurrent cases. Any systemic or ocular adverse effects of IVBI were reported ([Table 1]).
Table 1 Data of the patients

Click here to view



  Results Top


All patients demonstrated resolution of neurosensory detachment and improvement in BCVA.

In group A, the mean age of patients was 43.6 years (range, 23–52 years), there were 11 (57.89%) males and eight (42.10%) females, and the mean follow-up period was 9.2 months (range, 7–18) months. The mean log MAR visual acuity improved from 0.8 to 0.40 after 3 months of follow-up. The mean baseline CMT was 466 µm (range, 358–576 µm), which decreased to 309 µm (range, 268–356 µm) after 6 weeks, with statistically significance difference change from the baseline, and to 247 µm (range, 225–319 µm) after 3 months, with statistically significance difference change from the baseline (P<0.001).

In group B, the mean age of patients was 39.7 years (range, 42–57 years), there were nine (52.94%) males and eight (47.05%) females, and the mean follow-up period was 9.1 months (range, 6–16 months). The mean log MAR visual acuity improved from 1.00 to 0.40 after 3 months of follow-up. The mean baseline CMT was 454 µm (range, 334–567 µm), which decreased to 312 µm (range, 264–359 µm) after 6 weeks, with statistically significance difference change from the baseline, and to 252 µm (range, 232–338 µm) after 3 months, with statistically significance difference change from the baseline (P<0.001).

After 3 months of follow-up period, there was no significant difference in mean CMT between booth groups (247 vs. 252 µm). The mean baseline visual acuity improved in both groups without significant difference between them. No serious adverse effects have been observed in both groups. Three cases of acute type became chronic at the end of follow-up period.


  Discussion Top


CSCR is a self-limited condition characterized by idiopathic serous detachment of the neurosensory retina [4]. Many studies suggest that acetazolamide, laser photocoagulation, or intravitreal anti-VEGF injections can be used. Some authors have supported the benefit of early treatment of CSCR. These studies propose that the potential advantage of early resolution may be mediated by a lower rate of RPE degeneration in treated eyes [10],[18].

CSCR may be divided into two distinct clinical presentations. Classically, acute type is diagnosed by one or more discrete isolated leaks at the level of the RPE on fluorescein angiography. Chronic type is characterized by neurosensory retinal detachment overlying areas of RPE atrophy [25].

Some authors reported that foveal atrophy in CSCR is associated with reduction of visual acuity despite resolution of serous detachment, and hence reattachment within 4 months of onset is considered a relevant therapeutic target because prolonged detachment is associated with photoreceptor atrophy [26]. Treatment with acetazolamide might shorten the duration of the disease without influencing the final visual acuity or recurrence rate [10].

Some authors reported that laser photocoagulation was effective in shortening the duration of CSCR and reducing the recurrence rate, whereas others reported no definite advantage in terms of the final vision or recurrence [19]. In the current study, in group A ([Figure 1] and [Figure 2]), the mean baseline visual acuity improved from 0.80 to 0.40 (log MAR) after 3 months of follow-up. The mean baseline CMT was 466 µm (range, 358–576 µm), which decreased to 309 µm (range, 268–356 µm) after 6 weeks, with statistically significance difference change from the baseline and to 247 µm (range, 225–319 µm) after 3 months, with statistically significance difference change from the baseline.
Figure 1 A 35-year-old male patient with bilateral CSCR treated by bilateral macular grid laser. Images taken 6 months after initial presentation and macular grid laser treatment. The images show partial resolution of neurosensory detachment in his Right eye and complete resolution of the neurosensory detachment in the left one. (a, b, c, and d) Fundus photography, red free picture and FA of the right eye showing the laser marks. (e and f) OCT pictures of the right macula with residual detachment (g and h) OCT pictures of the left macula with resolution of detachment. (i, j, k, and l) Fundus photography, red free picture, and FA of the right eye with laser marks. CSCR, central serous chorioretinopathy; FA, fluorescein angiography; OCT, optical coherence tomography.

Click here to view
Figure 2 A 39-year-old female patient with right acute CSCR treated with macular grid laser. (a and b) OCT macula done at the first visit with marked sensory neural retinal detachment (SNRD); the CMT (±510 μm). (c and d) Fundus photography and red free fundus at the first visit. (e and f) OCT macula done after 3 months with partially resolved SRF; the CMT (±303 μm). (g and h) Fundus photography and red free fundus after 3 months with macular grid laser marks and decreased area of CSCR. CMT, central macular thickness; CSCR, central serous chorioretinopathy; OCT, optical coherence tomography; SRF, subretinal fluid.

Click here to view


In group B patients ([Figure 3]), the mean baseline visual acuity improved from 1.00 to 0.40 log MAR after 3 months of follow-up. The mean baseline CMT was 454 µm (range, 334–567 µm), which decreased to 312 µm (range, 264–359 µm) after 6 weeks, with statistically significance difference change from the baseline and to 252 µm (range, 232–338 µm) after 3 months, with statistically significance difference change from the baseline.
Figure 3 A 25-year-old male patient with right acute CSCR treated by IVBI. (a, b, c, and d) Fundus photography, red free fundus photography, and FA at initial presentation. (e and f) OCT images of the macula at the initial visit with CMT (±487 μm). (g and h) OCT images of the macula at 3-month follow-up visit with CMT (±312 μm), with resolution of SRF. CMT, central macular thickness; CSCR, central serous chorioretinopathy; FA, fluorescein angiography; IVBI, intravitreal bevacizumab injection; OCT, optical coherence tomography; SRF, subretinal fluid.

Click here to view


Torres-Soriano and colleagues reported in a study of six eyes (five chronic and one recurrent CSCR) that visual acuity improved in all cases by 1 month after intravenous injection of 2.5 mg Avastin and remained stable until the third month. The BCVA improved from 20/200 at baseline to 20/100 at 1 month and 20/50 at 3 months. They observed decreased neurosensory retinal and RPE detachment on OCT. The retinal thickness decreased from 375.83±92.34 to 252.5±58.28 µm at 1 month and 223±69.5 µm at 3 months after treatment. There was a decrease in fluorescein leakage. No adverse events developed [27].

Some authors reported in a series of 10 eyes of 10 patients with acute CSCR that all patients showed resolution of neurosensory detachment, and improvement in visual acuity and symptoms within 1 month. At 6 months, the mean BCVA (log MAR) had improved from 0.32 to 0.04, which was statistically significant (P=0.007). No recurrence was observed during the 6-month follow-up [28].

Another study done by Schaal and colleagues included 12 eyes with chronic CSCR in which patients received 2±1 intravitreal injections of bevacizumab 2.5 mg on average during a follow-up of 24±14 weeks. Mean BCVA increased by 2±2 lines; the change in BCVA (log MAR) was significant (P<0.02). Mean central retinal thickness decreased significantly over follow-up (P<0.05), with six (50%) patients showing complete resolution of SRF [2].In a retrospective comparative study, records of 45 patients with CSCR were reviewed. Twenty-two patients received IVB (1.25 mg/0.05 ml), whereas 23 patients were observed. The study concluded no significant difference between IVBI and observation [29]. This result can be explained by low dose of Avastin in comparison with the current study.

Another series reviewed four clinical controlled studies using the meta-analysis. The IVBI group achieved better BCVA at a follow-up of 6 months. However, the analysis showed that there were no significant differences of BCVA at 6 months after injection between IVB group and the observation group. This meta-analysis failed to verify the positive effect of IVB in CSCR [30].

A recent comparative study concluded that subthreshold micropulse diode laser photocoagulation to area of active leak appears to be a safe and effective modality to treat nonresolving CSCR. The outcome was superior in terms of visual recovery and complete resolution of SRF as compared with bevacizumab and suggested that IVBI may be useful as an adjunct rather than for primary therapy [31],[32].


  Conclusion Top


Both macular grid laser and IVBI for CSCR can lead to improvements of visual acuity and hasten recovery period. Macular grid laser may be considered as effective as anti-VEGF for treatment of CSCR. More studies using larger scales may be needed to clarify the uncertain relationship between pathogenesis and results of treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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