e21
Correspondence
may help on this issue. However, many other variables may play a role in the development of OAG after vitrectomy, and they should be considered. For instance, we believe that, rather than excluding the use of tamponading agents, it would be interesting to investigate whether their effect may facilitate OAG (i.e., by comparing air versus gas tamponade in macular hole surgery). Concerning bias reduction in future studies, randomization may also be critical to control for age, gender, behaviors, familiar history, and other known and as yet unknown possible confounding factors for OAG after vitrectomy. Finally, the pathophysiology of this condition needs further investigation as well. The predisposing role of cataract surgery requires confirmation because it was analyzed only in retrospective series with contrasting results. Furthermore, also the possible effect of oxidative stress generated by vitrectomy at the level of retinal ganglion cells should be explored. Hopefully, future well-designed studies will clarify many of these challenging issues. We trust we have answered the authors’ concerns satisfactorily. Andrea Govetto, MD* Ramón Domínguez, MD* María L. Landaluce, MD* María T. Alves, MStat† Ramón Lorente, PhD* †Biostatistics, Ourense University Hospital Ourense, Spain None of the authors have any financial/conflicting interests to disclose. References 1. Govetto A, Dominguez R, Landaluce M, et al. Prevalence of open angle glaucoma in vitrectomized eyes: a cross sectional study. Retina 2014;34:1623–1629. 2. Siegfried CJ, Shui YB, Holekamp NM, et al. Oxygen distribution in the human eye: relevance to the etiology of open-angle glaucoma after vitrectomy. Invest Ophthalmol Vis Sci 2010;51: 5731–5738. 3. Beebe DC, Shui YB, Siegfried CJ, et al. Preserve the (intraocular) environment: the importance of maintaining normal oxygen gradients in the eye. Jpn J Ophthalmol 2014;58:225–231. 4. Miki A, Medeiros FA, Weinreb RN, et al. Rates of retinal nerve fiber layer thinning in glaucoma suspect eyes. Ophthalmology 2014;121:1350–1358. 5. Jee D, Hong SW, Jung YH, Ahn MD. Interocular retinal nerve fiber layer thickness symmetry value in normal young adults. J Glaucoma 2014;23:125–131. 6. Mwanza JC, Durbin MK, Budenz DL. Interocular symmetry in peripapillary retinal nerve fiber layer thickness measured with the cirrus HD-OCT in healthy eyes. Am J Ophthalmol 2011; 151:514–521.
7. Budenz DL. Symmetry between the right and left eyes of the normal retinal nerve fiber layer measured with optical coherence tomography (an AOS thesis). Trans Am Ophthalmol Soc 2008; 106:252–275. 8. Alasil T, Wang K, Keane PA, et al. Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography. J Glaucoma 2013;22: 532–541. 9. Pierro L, Gagliardi M, Iuliano L, et al. Retinal nerve fiber layer thickness reproducibility using seven different OCT instruments. Invest Ophthalmol Vis Sci 2012;53: 5912–5920. 10. Lalezary M, Shah RJ, Reddy RK, et al. Prospective retinal and optic nerve vitrectomy evaluation (PROVE) study: twelvemonth findings. Ophthalmology 2014;121:1983–1989.
Correspondence To the Editor: We have read with interest the article “Thrombophilic risk factors are uncommon in young patients with retinal vein occlusion” published by Ahluwalia et al.1 The authors study the thrombotic factors in young patients with retinal vein occlusion. Interestingly, they conclude that these thrombophilia risk factors are not commonly associated with this condition and, moreover, there is a need to search other etiological factors for retinal vein occlusion, especially in younger patients. Branch retinal vein occlusion (BRVO) is not a rare disease with an incidence of 0.5% to 1.2%.2 Different risk factors, including hypertension, diabetes mellitus, hyperlipidemia, thrombophilia and hypercoagulation, medications, systemic and inflammatory disorders, and ocular conditions, have been shown to be associated with BRVO. However, their role is controversial, especially in young patients with BRVO. In this sense, it has been previously described that sharp bending of the veins is frequently seen at the arteriovenous crossing without compression.3 Johnson et al4 reported the evidence of vitreoretinal traction at the obstruction site on the involved vein in three cases of BRVO. It has also described a strong association between BRVO and posterior tractional retinal breaks, which are almost exclusively found in the distribution of the occluded vessel or even the avulsion of the affected vessel.5,6 We also reported the possible pathogenetic role of vitreovascular traction at the obstruction site in the etiology of an impending BRVO in a young woman.7 Likewise, we recently determined the incidence of vitreoretinal traction in patients diagnosed with BRVO by means of spectral domain optical coherence tomography directed to the occlusion site. We observed
e22
RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES 2015 VOLUME 35 NUMBER 3
vitreovascular traction at this point in 25% of BRVO cases, whereas none of the cases revealed vitreovascular traction in the correspondent arteriovenous crossing site of the same vessel segment of the fellow eye.8 Therefore, vitreovascular traction in the occlusion site was significantly associated with BRVO. Furthermore, B-scan ultrasonography showed that the posterior vitreous cortex remained more frequently attached in eyes with BRVO compared with unaffected fellow eyes. Curiously, prothrombin activity was significantly increased in BRVO patients without vitreovascular traction at the occlusion site compared with those presenting with vitreous traction.8 In conclusion, vitreoretinal traction might play an important role in some cases of BRVO, especially in young patients, whose vitreous cortex remains more frequently attached, suggesting that it could be a cofactor in the pathogenesis of BRVO. Francisco J. Ascaso, MD, PhD*†‡ Esteban Padgett, MD, PhD* Andrzej Grzybowski, MD, PhD§¶ *Department of Ophthalmology, “Lozano Blesa” University Clinic Hospital, Zaragoza, Spain †School of Medicine, University of Zaragoza Zaragoza, Spain ‡Aragon Health Sciences Institute, Zaragoza, Spain §Department of Ophthalmology, Poznan City Hospital, Poznan, Poland ¶University of Warmia and Mazury, Olsztyn, Poland None of the authors have any financial/conflicting interests to disclose. References 1. Ahluwalia J, Sandeep R, Varma S, et al. Thrombophilic risk factors are uncommon in young patients with retinal vein occlusion. Retina. 2014 Oct 8. [Epub ahead of print] doi: 10. 1097/IAE.0000000000000366. 2. Jaulim A, Ahmed B, Khanam T, Chatziralli IP. Branch retinal vein occlusion: epidemiology, pathogenesis, risk factors, clinical features, diagnosis, and complications. An update of the literature. Retina 2013;33:901–910. 3. Jefferies P, Clemett R, Day T. An anatomical study of retinal arteriovenous crossings and their role in the pathogenesis of retinal branch vein occlusions. Aust N Z J Ophthalmol 1993;21:213–217. 4. Johnson TM, Vaughn CH, Glaser BM. Branch retinal vein occlusion associated with vitreoretinal traction. Can J Ophthalmol 2006;41:600–602. 5. Singh M, Dhir L, Kon C, Rassam S. Tractional retinal break and rhegmatogenous retinal detachment consequent to branch retinal vein occlusion. Eye (Lond) 2006;20:1326–1327. 6. Joondeph HC, Joondeph BC. Posterior tractional retinal breaks complicating BRVO. Retina 1998;8:136–140. 7. Ascaso FJ, Huerva V. Vitreoretinal traction in impending branch retinal vein occlusion: a pathogenetic role? Thromb Haemost 2012;108:208–209.
8. Ascaso FJ, Padgett E, Núñez E, et al. Branch retinal vein occlusion and vitreovascular traction: a preliminary spectral domain OCT case-control study. Graefes Arch Clin Exp Ophthalmol 2014; 252:375–381.
Reply To the Editor: As stated by Ascaso et al, the etiology in young individuals with branch retinal vein occlusion and central retinal vein occlusion is likely to be multifactorial including genetic, environmental, and local factors. The systemic prothrombotic factors are unlikely to play a sole role in the causation as has been shown both in ours and in many other studies including meta-analyses.1–4 As has been reported by the Ascaso et al, a probable underevaluated cause for branch retinal vein occlusion might be local mechanical factors in individuals who lack the conventional causes for retinal vein occlusion.5 Virchow’s triad that describes the three broad categories of factors (hypercoagulable factors in the blood, endothelial injury, and turbulence/stasis), which contribute to thrombosis, is indispensable for explaining thrombosis at any site including the retinal vessels. Our study addressed the contents of blood that may favor a hypercoagulable state, and Ascaso et al have highlighted the other important aspect of the triad pertaining to blood flow. Vitreovascular traction by altering the laminar blood flow and creating turbulence is expected to change the flow dynamics and predispose to formation of thrombi locally. The significant increase in prothrombin activity in branch retinal vein occlusion patients without vitreoretinal traction at the occlusion site compared with those presenting with vitreous traction in the authors’ study is an interesting observation; however, we were unable to demonstrate an increase in prothrombin time, and therefore prothrombin activity in our cases. However, it would have been interesting to know if these patients had higher prothrombin levels because the prothrombin mutation, G20210A, which causes hyperprothrombinemia is known to occur almost exclusively in the whites. Therefore, the importance of causative factors in branch retinal vein occlusion and central retinal vein occlusion vary not only with demographic but also with geographic factors and predominant lifestyle patterns. Young individuals with retinal vessel occlusion probably represent a separate subset of patients in whom different set of etiologies may be operating and need to be evaluated thoroughly by methods including spectral domain optical coherence tomography as well as B-scan ultrasonography. Furthermore, appropriately designed experimental
Correspondence
may help on this issue. However, many other variables may play a role in the development of OAG after vitrectomy, and they should be considered. For instance, we believe that, rather than excluding the use of tamponading agents, it would be interesting to investigate whether their effect may facilitate OAG (i.e., by comparing air versus gas tamponade in macular hole surgery). Concerning bias reduction in future studies, randomization may also be critical to control for age, gender, behaviors, familiar history, and other known and as yet unknown possible confounding factors for OAG after vitrectomy. Finally, the pathophysiology of this condition needs further investigation as well. The predisposing role of cataract surgery requires confirmation because it was analyzed only in retrospective series with contrasting results. Furthermore, also the possible effect of oxidative stress generated by vitrectomy at the level of retinal ganglion cells should be explored. Hopefully, future well-designed studies will clarify many of these challenging issues. We trust we have answered the authors’ concerns satisfactorily. Andrea Govetto, MD* Ramón Domínguez, MD* María L. Landaluce, MD* María T. Alves, MStat† Ramón Lorente, PhD* †Biostatistics, Ourense University Hospital Ourense, Spain None of the authors have any financial/conflicting interests to disclose. References 1. Govetto A, Dominguez R, Landaluce M, et al. Prevalence of open angle glaucoma in vitrectomized eyes: a cross sectional study. Retina 2014;34:1623–1629. 2. Siegfried CJ, Shui YB, Holekamp NM, et al. Oxygen distribution in the human eye: relevance to the etiology of open-angle glaucoma after vitrectomy. Invest Ophthalmol Vis Sci 2010;51: 5731–5738. 3. Beebe DC, Shui YB, Siegfried CJ, et al. Preserve the (intraocular) environment: the importance of maintaining normal oxygen gradients in the eye. Jpn J Ophthalmol 2014;58:225–231. 4. Miki A, Medeiros FA, Weinreb RN, et al. Rates of retinal nerve fiber layer thinning in glaucoma suspect eyes. Ophthalmology 2014;121:1350–1358. 5. Jee D, Hong SW, Jung YH, Ahn MD. Interocular retinal nerve fiber layer thickness symmetry value in normal young adults. J Glaucoma 2014;23:125–131. 6. Mwanza JC, Durbin MK, Budenz DL. Interocular symmetry in peripapillary retinal nerve fiber layer thickness measured with the cirrus HD-OCT in healthy eyes. Am J Ophthalmol 2011; 151:514–521.
7. Budenz DL. Symmetry between the right and left eyes of the normal retinal nerve fiber layer measured with optical coherence tomography (an AOS thesis). Trans Am Ophthalmol Soc 2008; 106:252–275. 8. Alasil T, Wang K, Keane PA, et al. Analysis of normal retinal nerve fiber layer thickness by age, sex, and race using spectral domain optical coherence tomography. J Glaucoma 2013;22: 532–541. 9. Pierro L, Gagliardi M, Iuliano L, et al. Retinal nerve fiber layer thickness reproducibility using seven different OCT instruments. Invest Ophthalmol Vis Sci 2012;53: 5912–5920. 10. Lalezary M, Shah RJ, Reddy RK, et al. Prospective retinal and optic nerve vitrectomy evaluation (PROVE) study: twelvemonth findings. Ophthalmology 2014;121:1983–1989.
Correspondence To the Editor: We have read with interest the article “Thrombophilic risk factors are uncommon in young patients with retinal vein occlusion” published by Ahluwalia et al.1 The authors study the thrombotic factors in young patients with retinal vein occlusion. Interestingly, they conclude that these thrombophilia risk factors are not commonly associated with this condition and, moreover, there is a need to search other etiological factors for retinal vein occlusion, especially in younger patients. Branch retinal vein occlusion (BRVO) is not a rare disease with an incidence of 0.5% to 1.2%.2 Different risk factors, including hypertension, diabetes mellitus, hyperlipidemia, thrombophilia and hypercoagulation, medications, systemic and inflammatory disorders, and ocular conditions, have been shown to be associated with BRVO. However, their role is controversial, especially in young patients with BRVO. In this sense, it has been previously described that sharp bending of the veins is frequently seen at the arteriovenous crossing without compression.3 Johnson et al4 reported the evidence of vitreoretinal traction at the obstruction site on the involved vein in three cases of BRVO. It has also described a strong association between BRVO and posterior tractional retinal breaks, which are almost exclusively found in the distribution of the occluded vessel or even the avulsion of the affected vessel.5,6 We also reported the possible pathogenetic role of vitreovascular traction at the obstruction site in the etiology of an impending BRVO in a young woman.7 Likewise, we recently determined the incidence of vitreoretinal traction in patients diagnosed with BRVO by means of spectral domain optical coherence tomography directed to the occlusion site. We observed
e22
RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES 2015 VOLUME 35 NUMBER 3
vitreovascular traction at this point in 25% of BRVO cases, whereas none of the cases revealed vitreovascular traction in the correspondent arteriovenous crossing site of the same vessel segment of the fellow eye.8 Therefore, vitreovascular traction in the occlusion site was significantly associated with BRVO. Furthermore, B-scan ultrasonography showed that the posterior vitreous cortex remained more frequently attached in eyes with BRVO compared with unaffected fellow eyes. Curiously, prothrombin activity was significantly increased in BRVO patients without vitreovascular traction at the occlusion site compared with those presenting with vitreous traction.8 In conclusion, vitreoretinal traction might play an important role in some cases of BRVO, especially in young patients, whose vitreous cortex remains more frequently attached, suggesting that it could be a cofactor in the pathogenesis of BRVO. Francisco J. Ascaso, MD, PhD*†‡ Esteban Padgett, MD, PhD* Andrzej Grzybowski, MD, PhD§¶ *Department of Ophthalmology, “Lozano Blesa” University Clinic Hospital, Zaragoza, Spain †School of Medicine, University of Zaragoza Zaragoza, Spain ‡Aragon Health Sciences Institute, Zaragoza, Spain §Department of Ophthalmology, Poznan City Hospital, Poznan, Poland ¶University of Warmia and Mazury, Olsztyn, Poland None of the authors have any financial/conflicting interests to disclose. References 1. Ahluwalia J, Sandeep R, Varma S, et al. Thrombophilic risk factors are uncommon in young patients with retinal vein occlusion. Retina. 2014 Oct 8. [Epub ahead of print] doi: 10. 1097/IAE.0000000000000366. 2. Jaulim A, Ahmed B, Khanam T, Chatziralli IP. Branch retinal vein occlusion: epidemiology, pathogenesis, risk factors, clinical features, diagnosis, and complications. An update of the literature. Retina 2013;33:901–910. 3. Jefferies P, Clemett R, Day T. An anatomical study of retinal arteriovenous crossings and their role in the pathogenesis of retinal branch vein occlusions. Aust N Z J Ophthalmol 1993;21:213–217. 4. Johnson TM, Vaughn CH, Glaser BM. Branch retinal vein occlusion associated with vitreoretinal traction. Can J Ophthalmol 2006;41:600–602. 5. Singh M, Dhir L, Kon C, Rassam S. Tractional retinal break and rhegmatogenous retinal detachment consequent to branch retinal vein occlusion. Eye (Lond) 2006;20:1326–1327. 6. Joondeph HC, Joondeph BC. Posterior tractional retinal breaks complicating BRVO. Retina 1998;8:136–140. 7. Ascaso FJ, Huerva V. Vitreoretinal traction in impending branch retinal vein occlusion: a pathogenetic role? Thromb Haemost 2012;108:208–209.
8. Ascaso FJ, Padgett E, Núñez E, et al. Branch retinal vein occlusion and vitreovascular traction: a preliminary spectral domain OCT case-control study. Graefes Arch Clin Exp Ophthalmol 2014; 252:375–381.
Reply To the Editor: As stated by Ascaso et al, the etiology in young individuals with branch retinal vein occlusion and central retinal vein occlusion is likely to be multifactorial including genetic, environmental, and local factors. The systemic prothrombotic factors are unlikely to play a sole role in the causation as has been shown both in ours and in many other studies including meta-analyses.1–4 As has been reported by the Ascaso et al, a probable underevaluated cause for branch retinal vein occlusion might be local mechanical factors in individuals who lack the conventional causes for retinal vein occlusion.5 Virchow’s triad that describes the three broad categories of factors (hypercoagulable factors in the blood, endothelial injury, and turbulence/stasis), which contribute to thrombosis, is indispensable for explaining thrombosis at any site including the retinal vessels. Our study addressed the contents of blood that may favor a hypercoagulable state, and Ascaso et al have highlighted the other important aspect of the triad pertaining to blood flow. Vitreovascular traction by altering the laminar blood flow and creating turbulence is expected to change the flow dynamics and predispose to formation of thrombi locally. The significant increase in prothrombin activity in branch retinal vein occlusion patients without vitreoretinal traction at the occlusion site compared with those presenting with vitreous traction in the authors’ study is an interesting observation; however, we were unable to demonstrate an increase in prothrombin time, and therefore prothrombin activity in our cases. However, it would have been interesting to know if these patients had higher prothrombin levels because the prothrombin mutation, G20210A, which causes hyperprothrombinemia is known to occur almost exclusively in the whites. Therefore, the importance of causative factors in branch retinal vein occlusion and central retinal vein occlusion vary not only with demographic but also with geographic factors and predominant lifestyle patterns. Young individuals with retinal vessel occlusion probably represent a separate subset of patients in whom different set of etiologies may be operating and need to be evaluated thoroughly by methods including spectral domain optical coherence tomography as well as B-scan ultrasonography. Furthermore, appropriately designed experimental
