MANAGEMENT OF OPTIC DISK PIT– ASSOCIATED MACULAR DETACHMENT WITH TISSEEL FIBRIN SEALANT Khalid Al Sabti, FRCS(C),*†‡ Niranjan Kumar, FRCSEd,* David Robert Chow, FRCS(C),† Michael A. Kapusta, FRCS(C)†
Background: Optic disk pit–associated macular detachment is a challenging condition to treat. Many surgical methods have been used to treat this condition with varying degrees of success. Methods: We managed optic disk pit–associated macular detachment in three cases with pars plana vitrectomy, fluid–air exchange, drainage of subretinal fluid through the optic disk pit, application of Tisseel fibrin sealant (Baxter Healthcare Corporation, CA) to the optic disk pit, C3F8 gas injection, and postoperative prone positioning. Results: All three patients maintained flat maculae and had improved vision. Patient 3 had postoperative macular hole formation. This was managed successfully with pars plana vitrectomy, internal limiting membrane peeling, fluid–air exchange, and C3F8 gas injection. Conclusion: Our case series suggest that Tisseel fibrin sealant in conjunction with pars plana vitrectomy can be used successfully for management of optic pit disk–associated macular detachments. RETINAL CASES & BRIEF REPORTS 2:274 –277, 2008
medicine as a form of glue.3 We report three cases of optic disk pit–associated macular detachment successfully treated by PPV, application of Tisseel fibrin sealant to the pit, and gas injection. To our knowledge, this is the first reported successful use of Tisseel fibrin sealant in the management of optic disk pit–associated macular detachment.
From *Al Bahar Ophthalmology Center, Ibn Sina Hospital, Kuwait City, Kuwait; †Department of Ophthalmology, McGill University, Montreal, Quebec, Canada; and ‡Department of Surgery, Kuwait University, Jabriya, Kuwait.
O
ptic disk pit–associated macular detachment has attracted the attention of ophthalmologists for a long time. Spontaneous reattachment has been described in ⬇20% of cases; however, other patients continue to lose vision.1 Many surgical modalities have been used with varying degrees of success to treat this condition. These treatment options include sponge exoplant, laser, gas tamponade, pars plana vitrectomy (PPV), and the use of autologous platelets.2 Recently, Tisseel VH fibrin sealant (Baxter Healthcare Corporation, CA) has been used in many ophthalmological conditions and in other branches of
Case Reports Case 1 A 30-year-old French Canadian woman presented with a 6-month history of vision loss in the right eye. Ocular examination revealed visual acuity of 20/40 in the right eye and 20/20 in the left eye. Results of anterior segment examination were within normal limits. Fundus examination showed an optic disk pit with sensory retinal detachment of the macula and secondary retinal pigment epithelial changes in the right eye and normal findings for the left eye. She was observed for 4 months, at which time visual acuity dropped to 20/60 in the right eye. She underwent PPV, removal of the posterior hyaloid, fluid–air exchange, drainage of subretinal fluid (SRF) through the pit, endolaser treatment to the temporal juxtapapillary area, and injection of 14% C3F8 gas. The patient maintained a face down position for 3 weeks. Although the detachment was absent while gas tamponade was present, she had
Presented in part at the American Society of Retina Specialists 23rd Annual Meeting; July 16 –20, 2005; Montreal, Quebec, Canada. The authors have no financial interest in the products or procedures described in this study. Reprint requests: Niranjan Kumar, P.O. Box 1972, Ardiya 92400, Kuwait; e-mail: [email protected]
274
TISSEEL GLUE IN OPTIC DISK PIT–ASSOCIATED MACULAR DETACHMENT
275
Fig. 1. Preoperative fundus photograph showing the optic disk pit with macular detachment and a laser scar temporal to the disk in Case 1.
Fig. 2. Postoperative fundus photograph showing the flat macula in Case 1.
redetachment at 5 weeks postoperatively as the gas bubble receded. Visual acuity dropped to 20/200 in the right eye at that time. Pneumatic retinopexy with a second laser treatment to the temporal juxtapapillary area was attempted using 0.3 mL of 100% C3F8 gas and krypton red laser. Once again, the detachment flattened under the gas but reappeared as the bubble receded (Fig. 1). After discussion with the patient, repeated PPV was done with injection of human tissue fibrin glue (Tisseel VH fibrin sealant) over the optic disk pit. During PPV, absence of the posterior hyaloid was confirmed. Fluid–air exchange was done with drainage of SRF through the optic disk pit. During this step, it was interesting to note that while aspirating over the optic pit with a soft-tip silicone cannula the detachment slowly flattened. Meticulous drying of the optic disk pit and posterior pole was achieved to facilitate the use of Tisseel. The slow polymerizing form of human tissue fibrin glue was then applied directly over the optic nerve head. After a solid white fibrin sheet had formed across the optic disk, the air was exchanged with 14% C3F8 gas. The patient was positioned on her back for 2 hours postoperatively before prone positioning was commenced for 2 weeks. On the first postoperative day, fundus examination showed a dense white fibrin clot overlying the optic disk that disappeared over 1 week. The macula remained flat (Fig. 2), and vision gradually improved to 20/80 in the right eye at the 12-week follow-up. Six years postoperatively, the macula remained attached, and vision was maintained.
the left eye at the 12-week follow-up. Over 3 years, vision was maintained, and the macula remained flat.
Case 3 A 36-year-old Indian woman presented with a 2-week history of loss of vision in the left eye. Visual acuity was 20/20 in the right eye and 20/400 in the left eye. Fundus examination revealed an optic disk pit and macular detachment with cystic changes in the left eye (Fig. 3). Findings for the right eye were within normal limits. She underwent PPV, removal of the posterior hyaloid, fluid–air exchange, drainage of SRF through the optic disk pit (Fig. 4), application of fibrin glue to the optic disk (Fig. 5), and injection of 14% C3F8 gas. Postoperatively, the macula was flat for 2 weeks.
Case 2 A 34-year-old white woman presented complaining of a 1-month history of foggy vision in the left eye. Visual acuity was 20/20 in the right eye and 20/200 in the left eye. Ocular examination showed an optic disk pit with macular detachment in the left eye. Findings of right eye examination were within normal limits. She underwent PPV, removal of the posterior hyaloid, fluid–air exchange, drainage of SRF through the optic disk pit, application of fibrin glue to the optic disk, and 14% C3F8 gas injection. Postoperatively, the macula was flat. Visual acuity improved to 20/60 in
Fig. 3. Preoperative fluorescein angiogram showing the optic disk pit and macular detachment in Case 3.
276
RETINAL CASES & BRIEF REPORTSℜ
●
2008
●
VOLUME 2
●
NUMBER 4
Fig. 6. Postoperative fundus photograph showing the flat macula in Case 3. Fig. 4. Intraoperative photograph showing aspiration of subretinal fluid through the optic disk pit in Case 3.
She was then noted to have developed a macular hole with localized macular detachment. The macula remained detached in spite of maintaining strict prone positioning for an additional 2 weeks. There was no SRF communicating the optic disk pit with the macular detachment. Repeated PPV, internal limiting membrane peeling, fluid–air exchange, and 14% C3F8 gas injection were performed, which achieved total closure of the macular hole and reattachment of the macula (Fig. 6). One year postoperatively, visual acuity was 20/80 in the left eye. It is interesting that preoperative optical coherence tomography clearly showed the opening of the pit in the substance of the optic nerve head (Fig. 7). After surgery with fibrin glue, follow-up serial optical coherence tomography consistently showed closure of the optic disk pit (Fig. 8).
Fig. 5. Intraoperative photograph showing application of fibrin glue to the optic disk pit in Case 3.
Discussion Optic disk pit is a rare congenital anomaly. It may be complicated by macular detachment. Some patients with this condition may have spontaneous reattachment, but such an event is uncommon and occurs only after a long duration. Such long-standing macular detachments might be associated with irreversible visual loss due to macular pigment epithelial changes, cystic changes, and even macular hole formation.1 Many surgical options have been tried to treat this condition with variable success.2 In our case series, all three patients maintained flat maculae and had improved vision. We decided to apply fibrin glue to the optic disk intraoperatively, keeping the pathophysiology of optic disk pit–associated macular detachment in mind. There has been considerable controversy in the literature as to the
Fig. 7. Preoperative optical coherence tomography showing the optic disk pit in Case 3.
277
TISSEEL GLUE IN OPTIC DISK PIT–ASSOCIATED MACULAR DETACHMENT
Fig. 8. Postoperative optical coherence tomography showing the closed optic disk pit in Case 3.
pathophysiology of these detachments. Recent investigators showed that in at least some cases of optic disk pit–associated macular detachment the source of the SRF is through a dehiscence in the pit, allowing vitreous fluid to enter the subretinal space.4 This has been corroborated by the presence of subretinal gas and silicone oil seen in some patients who underwent PPV.5 In our patients, there was flattening of the retina intraoperatively during the fluid–air exchange by SRF drainage through the optic disk pit using a soft-tipped cannula, confirming the theory of direct communication with the vitreous. In addition, in Case 1, there was absence of detachment while the gas tamponade was present. This suggests that a direct communication between the vitreous and the subretinal space through the optic disk pit was the mechanism of detachment in our cases. This also explains the surgical success achieved in our cases with fibrin glue. Fibrin glue probably works by allowing a solid sheet of fibrin to tamponade the pit intraoperatively and by stimulating a wound healing process (gliosis) over the pit postoperatively. This was clearly demonstrated by optical coherence tomography. Human tissue fibrin glue is a biologically manufactured substance from pooled human plasma. It produces a physiologic clot through the interaction of fibrinogen, factor XIII, thrombin, and calcium. The advantages of the fibrin clot produced are that it is quite strong due to cross-linkage induced by the presence of factor XIII and is long acting due to the presence of aprotinin, which inhibits plasmin degradation of the fibrin clot. Tissue fibrin glue has been used successfully by multiple surgical subspecialties with no human toxicity.3 Tisseel fibrin sealant has been approved by the US Food & Drug Administration for use as a hemostatic agent in cardiopulmonary surgery and in the management of splenic injuries. It is a pooled blood product and is generally well tolerated by tissues. It has been shown to be safe and effective in neurosurgical procedures.6 Fibrin sealant was found not to have toxic effects on retinal function
or structure in a rabbit model.7 We did not observe retinal or optic nerve toxicity in any of our cases. Patient 3 developed a macular hole postoperatively. We believe that this was due to intraoperative damage to the cystic macula. However, long-term follow-up is needed to exclude retinal or optic nerve toxicity completely. We are unaware of any previous clinical use of this glue in vitreoretinal surgery. The major concern associated with this agent is that it is a pooled blood product and there may be a danger of viral transmission. To avoid this, it is manufactured using thoroughly screened plasma and a two-step vapor heating process. In the 10 million cases of use to date, there has not been a documented case of human viral transmission. From a vitreoretinal standpoint, there is a concern about the possibility of clot retraction and shearing damage to the peripapillary region. This was not a concern because this product lacks the thrombocytes inherent to the clot retraction process. In the absence of histopathologic confirmation, we cannot definitely prove that the success achieved was because of the direct use of fibrin glue. In conclusion, our experience suggests that Tisseel fibrin sealant can be used successfully for the management of optic disk pit–associated macular detachments. The uncommon nature of the condition does not lend well to the “gold standard” of a multicenter, randomized, control trial. Despite our small series, we are encouraged that the success we achieved might direct others to consider this product in the primary management of optic disk pit with sensory retinal detachment of the macula. Key words: fibrin glue, macular detachment, optic disk pit, pars plana vitrectomy. References 1.
2.
3.
4.
5.
6.
7.
Sobol WM, Blodi CF, Folk JC, Weingeist TA. Long term visual outcome in patients with optic nerve pit and serous retinal detachment of the macula. Ophthalmology 1990;97:1539–1542. Hirakata A, Okada AA, Hida T. Long term results of vitrectomy without laser treatment for macular detachment associated with an optic disc pit. Ophthalmology 2005;112:1430–1435. Koranyi G, Seregard S, Kopp ED. Cut and paste: a no suture, small incision approach to pterygium surgery. Br J Ophthalmol 2004;88:911–914. Brown GC, Shields JA, Goldberg RE. Congenital pits of the optic nerve head. II. Clinical studies in humans. Ophthalmology 1980;87:51–65. Johnson TM, Johnson MW. Pathogenic implications of subretinal gas migration through pits and atypical colobomas of the optic nerve. Arch Ophthalmol 2004;122:1793–1800. Kassam A, Horowitz M, Carrau R, et al. Use of Tisseel fibrin sealant in neurosurgical procedures: incidence of cerebrospinal fluid leaks and cost-effective analysis in a retrospective study. Neurosurgery 2003;52:1102–1105. Pardue MT, Hejny C, Gilbert JA, et al. Retinal function after subconjunctival injection of carboplatin in fibrin sealant. Retina 2004;24:776–782.
Background: Optic disk pit–associated macular detachment is a challenging condition to treat. Many surgical methods have been used to treat this condition with varying degrees of success. Methods: We managed optic disk pit–associated macular detachment in three cases with pars plana vitrectomy, fluid–air exchange, drainage of subretinal fluid through the optic disk pit, application of Tisseel fibrin sealant (Baxter Healthcare Corporation, CA) to the optic disk pit, C3F8 gas injection, and postoperative prone positioning. Results: All three patients maintained flat maculae and had improved vision. Patient 3 had postoperative macular hole formation. This was managed successfully with pars plana vitrectomy, internal limiting membrane peeling, fluid–air exchange, and C3F8 gas injection. Conclusion: Our case series suggest that Tisseel fibrin sealant in conjunction with pars plana vitrectomy can be used successfully for management of optic pit disk–associated macular detachments. RETINAL CASES & BRIEF REPORTS 2:274 –277, 2008
medicine as a form of glue.3 We report three cases of optic disk pit–associated macular detachment successfully treated by PPV, application of Tisseel fibrin sealant to the pit, and gas injection. To our knowledge, this is the first reported successful use of Tisseel fibrin sealant in the management of optic disk pit–associated macular detachment.
From *Al Bahar Ophthalmology Center, Ibn Sina Hospital, Kuwait City, Kuwait; †Department of Ophthalmology, McGill University, Montreal, Quebec, Canada; and ‡Department of Surgery, Kuwait University, Jabriya, Kuwait.
O
ptic disk pit–associated macular detachment has attracted the attention of ophthalmologists for a long time. Spontaneous reattachment has been described in ⬇20% of cases; however, other patients continue to lose vision.1 Many surgical modalities have been used with varying degrees of success to treat this condition. These treatment options include sponge exoplant, laser, gas tamponade, pars plana vitrectomy (PPV), and the use of autologous platelets.2 Recently, Tisseel VH fibrin sealant (Baxter Healthcare Corporation, CA) has been used in many ophthalmological conditions and in other branches of
Case Reports Case 1 A 30-year-old French Canadian woman presented with a 6-month history of vision loss in the right eye. Ocular examination revealed visual acuity of 20/40 in the right eye and 20/20 in the left eye. Results of anterior segment examination were within normal limits. Fundus examination showed an optic disk pit with sensory retinal detachment of the macula and secondary retinal pigment epithelial changes in the right eye and normal findings for the left eye. She was observed for 4 months, at which time visual acuity dropped to 20/60 in the right eye. She underwent PPV, removal of the posterior hyaloid, fluid–air exchange, drainage of subretinal fluid (SRF) through the pit, endolaser treatment to the temporal juxtapapillary area, and injection of 14% C3F8 gas. The patient maintained a face down position for 3 weeks. Although the detachment was absent while gas tamponade was present, she had
Presented in part at the American Society of Retina Specialists 23rd Annual Meeting; July 16 –20, 2005; Montreal, Quebec, Canada. The authors have no financial interest in the products or procedures described in this study. Reprint requests: Niranjan Kumar, P.O. Box 1972, Ardiya 92400, Kuwait; e-mail: [email protected]
274
TISSEEL GLUE IN OPTIC DISK PIT–ASSOCIATED MACULAR DETACHMENT
275
Fig. 1. Preoperative fundus photograph showing the optic disk pit with macular detachment and a laser scar temporal to the disk in Case 1.
Fig. 2. Postoperative fundus photograph showing the flat macula in Case 1.
redetachment at 5 weeks postoperatively as the gas bubble receded. Visual acuity dropped to 20/200 in the right eye at that time. Pneumatic retinopexy with a second laser treatment to the temporal juxtapapillary area was attempted using 0.3 mL of 100% C3F8 gas and krypton red laser. Once again, the detachment flattened under the gas but reappeared as the bubble receded (Fig. 1). After discussion with the patient, repeated PPV was done with injection of human tissue fibrin glue (Tisseel VH fibrin sealant) over the optic disk pit. During PPV, absence of the posterior hyaloid was confirmed. Fluid–air exchange was done with drainage of SRF through the optic disk pit. During this step, it was interesting to note that while aspirating over the optic pit with a soft-tip silicone cannula the detachment slowly flattened. Meticulous drying of the optic disk pit and posterior pole was achieved to facilitate the use of Tisseel. The slow polymerizing form of human tissue fibrin glue was then applied directly over the optic nerve head. After a solid white fibrin sheet had formed across the optic disk, the air was exchanged with 14% C3F8 gas. The patient was positioned on her back for 2 hours postoperatively before prone positioning was commenced for 2 weeks. On the first postoperative day, fundus examination showed a dense white fibrin clot overlying the optic disk that disappeared over 1 week. The macula remained flat (Fig. 2), and vision gradually improved to 20/80 in the right eye at the 12-week follow-up. Six years postoperatively, the macula remained attached, and vision was maintained.
the left eye at the 12-week follow-up. Over 3 years, vision was maintained, and the macula remained flat.
Case 3 A 36-year-old Indian woman presented with a 2-week history of loss of vision in the left eye. Visual acuity was 20/20 in the right eye and 20/400 in the left eye. Fundus examination revealed an optic disk pit and macular detachment with cystic changes in the left eye (Fig. 3). Findings for the right eye were within normal limits. She underwent PPV, removal of the posterior hyaloid, fluid–air exchange, drainage of SRF through the optic disk pit (Fig. 4), application of fibrin glue to the optic disk (Fig. 5), and injection of 14% C3F8 gas. Postoperatively, the macula was flat for 2 weeks.
Case 2 A 34-year-old white woman presented complaining of a 1-month history of foggy vision in the left eye. Visual acuity was 20/20 in the right eye and 20/200 in the left eye. Ocular examination showed an optic disk pit with macular detachment in the left eye. Findings of right eye examination were within normal limits. She underwent PPV, removal of the posterior hyaloid, fluid–air exchange, drainage of SRF through the optic disk pit, application of fibrin glue to the optic disk, and 14% C3F8 gas injection. Postoperatively, the macula was flat. Visual acuity improved to 20/60 in
Fig. 3. Preoperative fluorescein angiogram showing the optic disk pit and macular detachment in Case 3.
276
RETINAL CASES & BRIEF REPORTSℜ
●
2008
●
VOLUME 2
●
NUMBER 4
Fig. 6. Postoperative fundus photograph showing the flat macula in Case 3. Fig. 4. Intraoperative photograph showing aspiration of subretinal fluid through the optic disk pit in Case 3.
She was then noted to have developed a macular hole with localized macular detachment. The macula remained detached in spite of maintaining strict prone positioning for an additional 2 weeks. There was no SRF communicating the optic disk pit with the macular detachment. Repeated PPV, internal limiting membrane peeling, fluid–air exchange, and 14% C3F8 gas injection were performed, which achieved total closure of the macular hole and reattachment of the macula (Fig. 6). One year postoperatively, visual acuity was 20/80 in the left eye. It is interesting that preoperative optical coherence tomography clearly showed the opening of the pit in the substance of the optic nerve head (Fig. 7). After surgery with fibrin glue, follow-up serial optical coherence tomography consistently showed closure of the optic disk pit (Fig. 8).
Fig. 5. Intraoperative photograph showing application of fibrin glue to the optic disk pit in Case 3.
Discussion Optic disk pit is a rare congenital anomaly. It may be complicated by macular detachment. Some patients with this condition may have spontaneous reattachment, but such an event is uncommon and occurs only after a long duration. Such long-standing macular detachments might be associated with irreversible visual loss due to macular pigment epithelial changes, cystic changes, and even macular hole formation.1 Many surgical options have been tried to treat this condition with variable success.2 In our case series, all three patients maintained flat maculae and had improved vision. We decided to apply fibrin glue to the optic disk intraoperatively, keeping the pathophysiology of optic disk pit–associated macular detachment in mind. There has been considerable controversy in the literature as to the
Fig. 7. Preoperative optical coherence tomography showing the optic disk pit in Case 3.
277
TISSEEL GLUE IN OPTIC DISK PIT–ASSOCIATED MACULAR DETACHMENT
Fig. 8. Postoperative optical coherence tomography showing the closed optic disk pit in Case 3.
pathophysiology of these detachments. Recent investigators showed that in at least some cases of optic disk pit–associated macular detachment the source of the SRF is through a dehiscence in the pit, allowing vitreous fluid to enter the subretinal space.4 This has been corroborated by the presence of subretinal gas and silicone oil seen in some patients who underwent PPV.5 In our patients, there was flattening of the retina intraoperatively during the fluid–air exchange by SRF drainage through the optic disk pit using a soft-tipped cannula, confirming the theory of direct communication with the vitreous. In addition, in Case 1, there was absence of detachment while the gas tamponade was present. This suggests that a direct communication between the vitreous and the subretinal space through the optic disk pit was the mechanism of detachment in our cases. This also explains the surgical success achieved in our cases with fibrin glue. Fibrin glue probably works by allowing a solid sheet of fibrin to tamponade the pit intraoperatively and by stimulating a wound healing process (gliosis) over the pit postoperatively. This was clearly demonstrated by optical coherence tomography. Human tissue fibrin glue is a biologically manufactured substance from pooled human plasma. It produces a physiologic clot through the interaction of fibrinogen, factor XIII, thrombin, and calcium. The advantages of the fibrin clot produced are that it is quite strong due to cross-linkage induced by the presence of factor XIII and is long acting due to the presence of aprotinin, which inhibits plasmin degradation of the fibrin clot. Tissue fibrin glue has been used successfully by multiple surgical subspecialties with no human toxicity.3 Tisseel fibrin sealant has been approved by the US Food & Drug Administration for use as a hemostatic agent in cardiopulmonary surgery and in the management of splenic injuries. It is a pooled blood product and is generally well tolerated by tissues. It has been shown to be safe and effective in neurosurgical procedures.6 Fibrin sealant was found not to have toxic effects on retinal function
or structure in a rabbit model.7 We did not observe retinal or optic nerve toxicity in any of our cases. Patient 3 developed a macular hole postoperatively. We believe that this was due to intraoperative damage to the cystic macula. However, long-term follow-up is needed to exclude retinal or optic nerve toxicity completely. We are unaware of any previous clinical use of this glue in vitreoretinal surgery. The major concern associated with this agent is that it is a pooled blood product and there may be a danger of viral transmission. To avoid this, it is manufactured using thoroughly screened plasma and a two-step vapor heating process. In the 10 million cases of use to date, there has not been a documented case of human viral transmission. From a vitreoretinal standpoint, there is a concern about the possibility of clot retraction and shearing damage to the peripapillary region. This was not a concern because this product lacks the thrombocytes inherent to the clot retraction process. In the absence of histopathologic confirmation, we cannot definitely prove that the success achieved was because of the direct use of fibrin glue. In conclusion, our experience suggests that Tisseel fibrin sealant can be used successfully for the management of optic disk pit–associated macular detachments. The uncommon nature of the condition does not lend well to the “gold standard” of a multicenter, randomized, control trial. Despite our small series, we are encouraged that the success we achieved might direct others to consider this product in the primary management of optic disk pit with sensory retinal detachment of the macula. Key words: fibrin glue, macular detachment, optic disk pit, pars plana vitrectomy. References 1.
2.
3.
4.
5.
6.
7.
Sobol WM, Blodi CF, Folk JC, Weingeist TA. Long term visual outcome in patients with optic nerve pit and serous retinal detachment of the macula. Ophthalmology 1990;97:1539–1542. Hirakata A, Okada AA, Hida T. Long term results of vitrectomy without laser treatment for macular detachment associated with an optic disc pit. Ophthalmology 2005;112:1430–1435. Koranyi G, Seregard S, Kopp ED. Cut and paste: a no suture, small incision approach to pterygium surgery. Br J Ophthalmol 2004;88:911–914. Brown GC, Shields JA, Goldberg RE. Congenital pits of the optic nerve head. II. Clinical studies in humans. Ophthalmology 1980;87:51–65. Johnson TM, Johnson MW. Pathogenic implications of subretinal gas migration through pits and atypical colobomas of the optic nerve. Arch Ophthalmol 2004;122:1793–1800. Kassam A, Horowitz M, Carrau R, et al. Use of Tisseel fibrin sealant in neurosurgical procedures: incidence of cerebrospinal fluid leaks and cost-effective analysis in a retrospective study. Neurosurgery 2003;52:1102–1105. Pardue MT, Hejny C, Gilbert JA, et al. Retinal function after subconjunctival injection of carboplatin in fibrin sealant. Retina 2004;24:776–782.
