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ORIGINAL ARTICLE
Year : 2013  |  Volume : 5  |  Issue : 1  |  Page : 28-33

Retinal cryotherapy in diabetic vitreous hemorrhage


1 Department of Eye Surgery, BooAli Teaching Hospital, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
2 Department of Eye Surgery, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran

Date of Web Publication21-Sep-2013

Correspondence Address:
Ahmad Ahmadzadeh Amiri
BooAli Teaching Hospital, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari
Iran
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DOI: 10.4103/1858-540X.118644

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  Abstract 

Background: To evaluate the role of cryotherapy of anterior retina in preventing vitreous hemorrhage in patients with proliferative diabetic retinopathy (PDR). Materials and Methods: The patients were divided into two groups: (1) retinal cryotherapy without sufficient retinal laser treatment and (2) anterior peripheral retinal cryotherapy (ARC) in addition to sufficient panretinal laser treatment. The history and management of vitreous hemorrhage were recorded. Ocular examination and fluorescein angiographic findings for recovery of vision and presence of recurrent vitreous hemorrhage and neovascularization in the two groups were compared to determine the effectiveness of adjunct cryotherapy in PDR. Results:The rate of clearance of vitreous hemorrhage in groups 1 and 2 was 11 out of 13 (85%) and 15 out of 17 (88%), respectively (P = 0.717). In patients with cleared vitreous, the complete regression rate of neovacularization in groups 1 and 2 was 2 out of 11 (18%) and 8 out of 15 (53%), respectively (P < 0.05). Frequencies of the neovascular categories at different ocular sites in each group were similar, and no statistically significant difference was found (group 1, P = 0.884; group 2, P = 0.43). Comparison of corrected visual acuity on the last follow-up to corrected visual acuity before ARC gave the following results: 19 eyes had improved visual acuity of at least two lines, and visual recovery had similar distributions (group 1, P = 0.05; group 2, P = 0.085). Conclusions:It seems that ARC combined with photocoagulation might be a helpful adjunct procedure in PDR and to prevent recurrent vitreous hemorrhage.

Keywords: Panretinal photocoagulation, proliferative diabetic retinopathy, retinal cryotherapy, vitreous hemorrhage


How to cite this article:
Amiri AA, Esfahani MR. Retinal cryotherapy in diabetic vitreous hemorrhage. Sudanese J Ophthalmol 2013;5:28-33

How to cite this URL:
Amiri AA, Esfahani MR. Retinal cryotherapy in diabetic vitreous hemorrhage. Sudanese J Ophthalmol [serial online] 2013 [cited 2019 Sep 20];5:28-33. Available from: http://www.sjopthal.net/text.asp?2013/5/1/28/118644


  Introduction Top


Complications of proliferative diabetic retinopathy (PDR) are usually treated successfully by panretinal laser photocoagulation. It reduces the risk of severe visual loss in patients with high-risk PDR or severe nonproliferative diabetic retinopathy by 50%-60%. [1],[2] The efficacy of laser photocoagulation depends on clear ocular media and appropriately wide pupil that may be difficult to dilate. In diabetics, the clarity of media is more often compromised by cataract, vitreous hemorrhage (VH), or even after cataract-related thickened capsular membrane. Advances in surgical intervention have made it possible to perform intravitreal antiangiogenic injection and vitrectomy to prevent the complications of PDR; however, in special circumstances, these options are not feasible for some patients. [3],[4],[5],[6] The results of a recent study showed that intravitreal antiangiogenic therapy is a well-tolerated treatment option for PDR in carefully selected patients, but suggested that the application of this treatment may lead to tractional retinal detachment in 3.58%-5.2% of patients. [4],[5],[7] Thus, an alternative method of retinal ablation may be required in certain circumstances. Retinal cryotherapy is effective in treating and preventing proliferative diseases in retinopathy of prematurity and diabetics. [8],[9],[10],[11] Application of cryotherapy does not require a fully dilated pupil and clear ocular media. The wide field binocular indirect ophthalmoscopy of fundus allows to monitor the freeze is inherent to peripheral retina at any one moment while using the device. The procedure is easy and its instrument is readily available. Risks involved in retinal cryotherapy include infection, perforation of the eye with the anesthetic needle, bleeding, double vision, and glaucoma. All of these complications, however, are quite uncommon.

The purpose of this paper is to describe the efficacy of retinal cryotherapy on regression of proliferation in diabetic patients with PDR and ocular media opacity, for whom effective laser photocoagulation has not been feasible in Farabi Hospital, Tehran, Iran.


  Materials and Methods Top


This is an interventional case series conducted on diabetic patients with PDR and cloudy media. Nominated patients and eyes were obtained from a retina service of patients who were diagnosed with PDR. The presence and extent of diabetic high-risk fundus characteristics of the disk, macula, and periphery were assessed when possible. The presence of VH, defined as new vitreous or preretinal hemorrhage not observed on previous examinations, was recorded at baseline and on all visits during the follow-up period. The presence of active neovascularization of the disk and active neovascularization elsewhere was documented. Eyes were selected if they had no tractional retinal membrane involving the macula or optic nerve head, no use of anticoagulation routinely before this operation, and no indication for vitrectomy. Ultrasound examination was performed on the operated cases in a nonselective manner to detect any vitreoretinal traction. Informed consent was obtained from every patient. Preoperative, intraoperative, and postoperative data were collected for each patient; these included age, gender, study eye, type and duration of diabetes mellitus, general condition, and cryotherapy. Data regarding initial and final visual acuity, recovery of VH, regression of retinal neovascularization, and duration of postoperative follow-up were also compiled. The cases were divided into two groups: patients in group 1 had retinal cryotherapy without sufficient retinal laser treatment, and those in group 2 had retinal cryotherapy in addition to sufficient panretinal photocoagulation (PRP) extending to or beyond the vortex vein ampulae (equatorial region). [1] Our technique for transscleral peripheral retinal cryotherapy was as follows. A small peritomy was performed and local anesthetic agent was administered to the retrobulbar region through a bent catheter. Confluent retinal freezes were applied in two or three rows beginning at the ora serrata and extending posteriorly to the anterior equatorial region in all four quadrants. Approximately 8-10 retinal freeze thaw applications with 2.5-mm retinal cryoprobe were delivered under indirect ophthalmoscopic view and placed in each quadrant. Each application was stopped as soon as the retina turned white. In areas where VH did not permit visualization, the freeze thaw application was a similar duration. The time taken to produce the desired ice ball was measured during initial application and varied from 4 to 8 sec. Topical steroid, mydriatics, and antibiotic eye drops were administrated for all eyes postoperatively. Patients were visited at 1 week, 4 weeks, and then on a 2-monthly basis until at least 1 year. Snellen visual acuities were converted to decimal equivalents for statistical procedures. For the purpose of analysis, visual acuities of no light perception, light perception, hand motions, and counting fingers were assigned decimal values of 0.001, 0.005, 0.01, and 0.05, respectively. Visual acuities were expressed as logMAR equivalents for statistical comparisons.

The Statistical Package for Social Sciences for Windows (SPSS Inc., version 18.0, Chicago, IL, USA) was used for statistical analysis. Data comparisons were performed using analysis of variance with repeated measures. Alpha = 0.05 was the chosen significance level.


  Results Top


Thirty-one eyes of 24 patients undergoing peripheral retinal cryotherapy for PDR were included in our study. The patients' characteristics for each study group are listed in [Table 1]. Fourteen patients were females. In four male and two female patients, both eyes qualified for this study. The mean age of patients was 56.21 ± 11.93 years (mean ± SD; range, 29-75 years). The mean duration of diabetes mellitus at the time of ARC was 11.33 ± 6.75 years (range, 4-30 years). According to the medical chart history, six patients were on insulin and half of the patients had a history of hypertension. Except for the follow-up duration, none of the categories had a statistically significant difference between the two groups (P = 0.05).
Table 1: Clinical characteristics of patients in two groups

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Visual acuity data and ophthalmic fundus characteristics of the study eyes at baseline and the last follow-up are summarized in [Table 2].
Table 2: Results of peripheral retinal cryotherapy for diabetic vitreous hemorrhage

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Prominent VH was relatively common at baseline (66%). Three eyes had neovascularization of iris (NVI), four eyes had media haziness due to associated cataract, and two eyes had miotic pupil.

Among the 30 eyes with ocular neovascularization at baseline, only 7 (21%) were found to have retained it at the last follow-up. The pattern of prevalence at baseline and presence at final examination was similar for all patterns of neovascularization. In patients with cleared vitreous, the complete regression rates of neovacularization in groups 1 and 2 were 2 out of 11 (18%) and 8 out of 15 (53%), respectively (P < 0.05). Frequencies of the neovascular categories at the different ocular sites in each group were similar, and no statistically significant difference was found (group 1, P = 0.884; group 2, P = 0.43).

All eyes with NVI had an intraocular pressure within the accepted normal range at the last follow-up in both groups. So far, all eyes have remained pain-free, all showed regression of iris neovascularization, and all but one eye had an intraocular pressure within the accepted normal range without medication.

The clearance of VH rates in groups 1 and 2 were 11 out of 13 (85%) and 15 out of 17 (88%), respectively (P = 0.717). One case in group 2 received cryotherapy combined with additional laser photocoagulation for media cleared up. Three out of 30 eyes with PRC had persistent VH either at baseline or on follow-up. The VH eventually disappeared after vitrectomy. Further analysis revealed that healed and initial VH did not differ significantly between the two groups (P = 0.749).

One case in group 2 had tractional retinal detachment postoperatively. Two cases in each group required vitreous surgery; one of the vitrectomies was in eyes that had a tractional retinal detachment on follow-up.

Records of corrected visual acuity at the time of VH leading to ARC, at 1 week after ARC, and on the last follow-up after ARC were available for all 30 eyes. The mean baseline best-corrected visual acuity (BCVA) was logMAR = 1.57 ± 0.42, and the mean last follow-up BCVA was logMAR = 0.99 ± 0.49 (P < 0.0005). The median of corrected visual acuity before the ARC was hand motion (range LP to 20/100). One week after ARC, the median of corrected visual acuity was counting fingers (range, hand motions to 20/200). On the final follow-up after ARC, the median of corrected visual acuity was 20/200 (range, no light perception to 20/50) in each group [Figure 1] and [Figure 2].
Figure 1: LogMAR corrected visual acuity measurements before, 1 week after, and on the last follow-up after ARC

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Figure 2: The final difference in visual acuity between the two groups after ARC for 30 eyes. Visual acuities, measured with the patient's current correction or with best correction by refraction, are expressed as decimal
equivalents


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Comparison of corrected visual acuity on the last follow-up to corrected visual acuity before ARC yielded the following results: 19 (63%) eyes had improved visual acuity of at least two lines. Data for this comparison were available for all 30 eyes. The difference between visual acuity at the time of ARC and visual acuity on the last follow-up after ARC was statistically significant (Pearson Chi-square, P < 0.001), but similar between the two groups (group 1, P = 0.05; group 2, P = 0.085).


  Discussion Top


Recurrent VH occurs frequently in patients with complications of PDR and it may obscure media for laser photocoagulation. [12],[13],[14] PRP has been the mainstay for treating PDR, and its suppressive effect on retinal neovascularization has been well documented. However, substantial regression of new vessels may take weeks after completion of PRP, and in up to one-third of cases, new vessels continue to grow despite initial PRP. [15] Standard PRP alone may not be intensive enough to fully inhibit the production of angiogenic factors. Additional retinal ablation in the far peripheral area may further reduce the amount of angiogenic factors and minimize the chance of proliferation of neovascular tissue and VH. We chose cryotherapy over the other methods for anterior retina ablation due to its simplicity and safety.

Among our patients, transscleral peripheral retinal cryotherapy was successful in preventing further vitreous hemorrhaging in the majority of eyes (86%), and was not different among the two groups with or without laser photocoagulation, which is similar to the findings of Pauleikhoff et al. [16] and Daily et al. [9] (80% and 83%, respectively, without prior laser photocoagulation, and 75% with previous panretinal photocoagulation), but was relatively higher than the rate reported by Benedett et al,[17] . [16 (50%)].

In this series, neovascular regression was found in a high proportion of patients with cleared vitreous in group 2 (P = 0.007). Although proliferative changes were not prominent in the other group, no obvious VH was noted (P = 0.866). We believe that this finding may not be significant, as neovascularization will eventually become fibrotic and cease to be a source of hemorrhage over time.

In our trial, peripheral retinal cryotherapy improved final corrected visual acuity at least two lines in 19 out of 32 eyes (59%), similar to the rate reported by Pauleikhoff et al.[16] (60%), but relatively higher than the rates reported in other studies [Nikeghbali [18] (31.6%), Benedett et al.[17] (44%), and Daily et al.[19] (46%)].

Although some studies [17],[20] support the hypothesis that cryotherapy might be a helpful adjunct procedure in diabetic vitrectomy to inhibit fibrovascular ingrowths and to prevent recurrent VH, others [21] believe that cryotherapy of the sclerotomy sites does not reduce the risk of late postvitrectomy hemorrhage in diabetic eyes. The discrepancy in reports of cryotherapy effectiveness may be partly due to different criteria used to define study methods in different studies.

There are currently numerous reports on the adjunctive benefits of using antiangiogenic agents such as intravitreal triamcinolone acetonide and bevacizumab in preventing recurrent VH in diabetic eyes. [22],[23],[24] Intravitreal injection of 1.25 mg bevacizumab with PRP is associated with rapid regression of VH in more than 90% of cases and may diminish the need for vitrectomy. [25],[26] Nevertheless, intravitreal injections of bevacizumab (Avastin) harbors systemic and local adverse events in a minority of patients, including acute elevation of systemic blood pressure, cerebrovascular accident, myocardial infarction, bacterial endophthalmitis, tractional retinal detachment, and uveitis, in less than 3.5% of cases. [3],[4],[5] However, peripheral retinal cryotherapy has been shown to be more feasible and have less limitation, and consequently is favorable for selected diabetic patients. One of the potential flaws in this study is that the follow-up time varied among patients in the two groups. In fact, in this study, six patients were treated in two eyes at different times. Despite this fact, we believe the comparison among the two groups is still valid. Although ARC might be helpful in preventing PDR progression, this procedure, alone or in combination with laser photocoagulation, seemed less effective in preventing further repeated VH after establishment of fibrovascular tissue on retina. In our trial, we did not find any relationship between cryotherapy and morphologic patterns of the proliferation, or between these patterns and the occurrence of VH. It should be noted, however, that this might be due to the limited number of eyes that underwent cryotherapy.

In conclusion, this study indicates that poor regression of retinal neovascular tissue seems to correlate well with the development of recurrent VH, and it seems to support the hypothesis that anterior peripheral retinal cryotherapy (ARC) combined with photocoagulation might be a helpful adjunct procedure in PDR and to prevent recurrent VH. Establishing the latter statement requires further clinical trials evaluating the combination of this procedure with anterior retinal cryotherapy or photocoagulation.

 
  References Top

1.Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology 1981;88:583-600.  Back to cited text no. 1
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2.Doft BH, Blankenship GW. Single versus multiple treatment sessions of argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 1982;89:772-9.  Back to cited text no. 2
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3.Wu L, Martínez-Castellanos MA, Quiroz-Mercado H, Arevalo JF, Berrocal MH, Farah ME, et al. Twelve-month safety of intravitreal injections of bevacizumab (Avastin): Results of the Pan-American Collaborative Retina Study Group (PACORES). Graefes Arch Clin Exp Ophthalmol 2008;246:81-7.  Back to cited text no. 3
    
4.Arevalo JF, Sanchez JG, Lasave AF, Wu L, Maia M, Bonafonte S, et al. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture. J Ophthalmol 2011;2011:584238.  Back to cited text no. 4
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5.Arevalo JF, Maia M, Flynn HW Jr, Saravia M, Avery RL, Wu L, et al. Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol 2008;92:213-6.  Back to cited text no. 5
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6.Michels RG, Rice TA, Rice EF. Vitrectomy for diabetic vitreous hemorrhage. Am J Ophthalmol 1983;95:12-21.  Back to cited text no. 6
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8.Vernon SA, Cheng H. Panretinal cryotherapy in neovascular disease. Br J Ophthalmol 1988;72:401-5.  Back to cited text no. 8
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9.Daily MJ, Gieser RG. Treatment of proliferative diabetic retinopathy with panretinal cryotherapy. Ophthalmic Surg 1984;15:741-5.  Back to cited text no. 9
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10.Repka MX, Palmer EA, Tung B. Involution of retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol 2000;118:645-9.  Back to cited text no. 10
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11.Mills MD. Evaluating the Cryotherapy for Retinopathy of Prematurity Study (CRYO-ROP). Arch Ophthalmol 2007;125:1276-81.  Back to cited text no. 11
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12.Yan H, Cui J, Lu Y, Yu J, Chen S, Xu Y. Reasons for and management of postvitrectomy vitreous hemorrhage in proliferative diabetic retinopathy. Curr Eye Res 2010;35:308-13.  Back to cited text no. 12
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15.Randomized comparison of krypton versus argon scatter photocoagulation for diabetic disc neovascularization. The Krypton Argon Regression Neovascularization Study report number 1. Ophthalmology 1993;100:1655-64.  Back to cited text no. 15
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18.Nik Eghbali A. Cryotherapy in proliferative diabetic retinopathy. Iran Red Crescent Med J 2000;3:20-2.  Back to cited text no. 18
    
19.Yeh PT, Yang CM, Yang CH, Huang JS. Cryotherapy of the Anterior Retina and Sclerotomy Sites in Diabetic Vitrectomy to Prevent Recurrent Vitreous Hemorrhage. An Ultrasound Biomicroscopy Study. Ophthalmology 2005;112:2095-102.  Back to cited text no. 19
    
20.Neely KA, Scroggs MW, McCuen BW 2 nd . Peripheral retinal cryotherapy for postvitrectomy diabetic vitreous hemorrhage in phakic eyes. Am J Ophthalmol 1998;126:82-90.  Back to cited text no. 20
    
21.Entezari M, Ramezani A, Ahmadieh H, Bakhtiari P, Yaseri M, Soltani K. Cryotherapy of sclerotomy sites for prevention of late post-vitrectomy diabetic hemorrhage: A randomized clinical trial. Graefes Arch Clin Exp Ophthalmol 2010;248:13-9.  Back to cited text no. 21
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22.Faghihi H, Taheri A, Farahvash MS, Riazi Esfahani M, Taher Rajabi M. Intravitreal triamcinolone acetonide injection at the end of vitrectomy for diabetic vitreous hemorrhagea randomized, clinical trial. Retina 2008;28:1241-6.  Back to cited text no. 22
    
23.Rizzo S, Genovesi-Ebert F, Di Bartolo E, Vento A, Miniaci S, Williams G. Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR). Graefes Arch Clin Exp Ophthalmol 2008;246:837-42.  Back to cited text no. 23
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24.Lo WR, Kim SJ, Aaberg TM, Bergstrom C, Srivastava SK, Yan J, et al. Visual outcomes and incidence of recurrent vitreous hemorrhage after vitrectomy in diabetic eyes pretreated with bevacizumab (avastin). Retina 2009;29:926-31.  Back to cited text no. 24
    
25.Huang YH, Yeh PT, Chen MS, Yang CH, Yang CM. Intravitreal bevacizumab and panretinal photocoagulation for proliferative diabetic retinopathy associated with vitreous hemorrhage. Retina 2009;29:1134-40.  Back to cited text no. 25
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