834
Indian Journal of Ophthalmology
Vol. 62 No. 7
case serves to remind us to consider massive sub‑retinal and suprachoroidal hemorrhages as causes of secondary angle closure glaucoma, especially in patients with known AMD and PCV.
ranibizumab treatment provided superior visual acuity (VA) gains compared to PDT. In addition, among the non‑randomized studies published in the literature, patients with myopic CNV treated using anti‑VEGF agents were reported to have better mean VA compared to patients treated with PDT.[4]
Wei Kiong Ngo1, Kai Xiong Cheong1, Colin SH Tan1,2
However, we would like to highlight that PDT may result in good visual outcomes in carefully selected patients, especially those with extrafoveal CNV lesions where the laser spot can be adjusted to spare the fovea. In a study of 24 eyes with myopic CNV,[5] we found that among patients who were treated with foveal‑sparing PDT, 77.8% achieved VA of ≥ 20/40, with a mean final logMAR VA of 0.26. An additional factor influencing the outcome is size of the myopic CNV lesion. Tan et al.[4] reported that myopic CNV lesions with a greatest linear diameter (GLD) of ≤ 1000 µm had better outcomes compared to those with larger GLD. While we acknowledge the difficulty of making direct comparisons of results from different studies, it is interesting to note that the visual outcomes in our study were comparable to, or in some cases better than, those reported from studies using anti‑VEGF agents.[5]
National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore 1
Correspondence to: Dr. Colin SH Tan, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11, Jalan Tan Tock Seng, Singapore ‑308433. E‑mail: [email protected]
References 1. Williams GS, Anderson L, Eddyshaw D. Macular hemorrhage as a cause of acute angle closure. Indian J Ophthalmol 2013;61:683‑4. 2. Lim TH, Laude A, Tan CS. Polypoidal choroidal vasculopathy: An angiographic discussion. Eye (Lond) 2010;24:483‑90. 3. Tan CS, Wong HT, Lim BA, Hee OK, Lim TH. Polypoidal choroidal vasculopathy causing massive suprachoroidal haemorrhage. Eye (Lond) 2007;21:132‑3. 4. Tan CS, Ngo WK, Lim LW, Cheong KX, Lim TH. Outcomes of polypoidal choroidal vasculopathy treated with ranibizumab monotherapy. Br J Ophthalmol 2013;97:1357‑8. 5. Koh A, Lee WK, Chen LJ, Chen SJ, Hashad Y, Kim H, et al. Everest study: Efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina 2012;32:1453‑64. Access this article online Quick Response Code:
Website: www.ijo.in DOI: 10.4103/0301-4738.138176
Anti‑VEGF agents are associated with systemic risks such as cerebrovascular accidents and other arterial thromboembolic events, especially for patients with pre‑existing disease.[5] In addition, intravitreal injections carry the risk of infectious endophthalmitis.[5] Some patients are unwilling to accept either the systemic or ocular risks associated with anti‑VEGF agents, and for them, PDT may be a valuable modality of treatment. In conclusion, ophthalmologists may wish to consider PDT in cases where the fovea can be spared, and where anti‑VEGF agents are unsuitable or unacceptable to patients. It has been shown that extrafoveal CNV lesions occur in between 18.5 and 32% of myopic CNV patients.[5] Therefore, we believe that PDT may still have a useful role in the management of myopic CNV, if patients are carefully selected.
Milton C Chew 1, Colin S Tan1,2 Department of Ophthalmology, Tan Tock Seng Hospital, 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore 1
Treatment options for myopic CNV ‑ Is photodynamic therapy still relevant? Dear Sir, We read with interest the article by Manayeth et al. [1] describing the use of low‑fluence photodynamic therapy (PDT) to successfully treat a patient who developed myopic choroidal neovascularization (CNV) following laser in situ Keratomileusis (LASIK), as well as the comment by Gopal[2] on the efficacy of anti‑vascular endothelial growth factor (anti‑VEGF) agents compared to PDT in the treatment of CNV. The Ranibizumab and PDT [verteporfin] evaluation in myopic choroidal neovascularization (RADIANCE) study,[3] a randomized controlled trial comparing ranibizumab against verteporfin PDT for the treatment of myopic CNV, reported that
Correspondence to: Dr. Colin S Tan, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11, Jalan Tan Tock Seng, Singapore - 308433. E‑mail: [email protected]
References 1. Manayath GJ, Narendran V, Ganesh A, Arora S. Low‑fluence photodynamic therapy for early onset choroidalneovascular membrane following laser in situ keratomileusis. Indian J Ophthalmol 2012;60:584‑5. 2. Santhan Gopal KS. Low‑fluence PDT better than anti‑vascular endothelial growth factor. Indian J Ophthalmol 2013;61:691. 3. Wolf S, Balciuniene VJ, Laganovska G, Menchini U, Ohno‑Matsui K, Sharma T, et al. RADIANCE study group. RADIANCE: A randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology 2014;121:682‑92.e2. 4. Tan CS, Chew MC, Lim KH, Lim TH. Factors affecting visual outcome of myopic choroidal neovascularization treated with
July 2014 Letters to the Editor verteporfin photodynamic therapy. Int J Ophthalmol 2013;6:327‑30. 5. Tan CS, Chew MC, Lim TH. Comparison of foveal‑sparing with foveal‑involving photodynamic therapy for myopic choroidal neovascularization. Eye (Lond) 2014;28:17‑22. Access this article online Quick Response Code:
Website: www.ijo.in DOI: 10.4103/0301-4738.138174
Varied phenotype of Homocystinuria: Possible diagnostic error Dear Sir, There are several crucial points to be made regarding the diagnostic criteria for the diagnosis of homocystinuria (HCU) due to cystathionine β‑synthase (CβS) in a recent article.[1] The authors have provided a comprehensive ophthalmological examination on the two siblings described. However, the diagnosis of HCU seemed to be based mainly on mildly elevated homocysteine levels (16.02 and 18µmol/L) and the ocular findings in the 2 cases, without concurrent levels of methionine, cystine, or other confirmatory tests. The presence of typical clinical signs may lead to a suspicion of CβS deficiency, but definitive diagnosis depends on a severely raised total homocysteine (tHcy; >100-400µmol/L) with low methionine and cystine levels. The confirmation of diagnosis is by CβS enzymology in cultured skin fibroblast and/or molecular analysis.[2] Plasma B12 and folate are routinely checked for nutritional deficiencies which can cause mildly elevated tHcy similar to the levels reported. Upon diagnosis, a trial of pyridoxine (B6) is given to ascertain clinical B6 responsiveness, as there is no correlation between in vitro and in vivo responsiveness.[3] Intellectual abilities as reported on sibling 1 as having developmental delay is at odds with a further statement which makes the assumption of probable “B6 responsive type” in the siblings based on the “mild systemic involvement and normal intelligence.” The authors further conclude that having developed ectopia lentis by 8 years as yet another factor for diagnosing HCU based on Mulvihill et al.[4] As a co‑author of the quoted article, the conclusion drawn by the authors on our study having shown that “ectopia lentis in homocystinuria develops after 1 year and maximum by 8 years” is incorrect. Instead, Mulvihill et al. documented that a diagnosis of HCU was made at a median age of 4 years (range: 1.2-8) in 10 out of 14 cases in the late detected group. A further four cases had a median age of diagnosis for HCU of 12.8 years (range: 4-23). All 14 cases had lens subuxation/dislocation at a median age of HCU diagnosis of 6 years (range: 1.25-28 years).[4] Our study only documented
835
the age at which time a diagnosis of HCU was made and did not determine when exactly ectopia lentis had occur.[4] Timing of ectopia lentis is not a diagnostic criteria. The authors correctly surmised that superonasal subluxation is atypical of HCU, however, the diagnosis of HCU in the reported cases has yet to be confirmed correctly. In view of the abdominal hernias and ectopia lentis, it would be usual to rule out other causes such as Marfan syndrome and to properly confirm the diagnosis of HCU. Vitamin deficiencies should be looked for as a cause of mild hyperhomocysteinemia. In the presence of second degree consanguinity, it may be useful to look for other causes of developmental delay, if indeed present in Sibling 1. In summary, the diagnosis of HCU must be confirmed and not simply based on mild hyperhomocysteinemia and some clinical features. Ascribing atypical features to HCU is premature especially when there is no evidence of the diagnosis being confirmed in a recognized manner.
Sufin Yap Department of Inherited Metabolic Diseases, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield S10 2TH, United Kingdom Correspondence to: Prof Dr Sufin Yap, Department of Inherited Metabolic Diseases, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield S10 2TH, United Kingdom. E‑mail: [email protected]
References 1. Kaliaperumal S, Kumar KP; Bhuvaneshwari. Varied phenotypic presentations of Homocystinuria in two siblings. Indian J Ophthalmol 2014;62:93‑4. 2. Mudd SH, Levy HL, Kraus JP. Disorders of transsulfuration. In: Scriver CR, Baeudet AL, Sly WS , Valle D, Childs B, Kinzler KW , et al. editors. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw‑Hill; 2001. p. 2007‑54. 3. Yap S, Naughten E. Homocystinuria due to cystathionine β‑synthase deficiency in Ireland: 25 years’ experience of a newborn screened and treated population with reference to clinical outcome and biochemical control. J Inher Metab Dis 1998;21:738‑47. Available from: http://dx.doi.org/10.1023/A: 1005445132327 [Last accessed on 2014 Mar 04]. 4. Mulvihill A, Yap S, O’Keefe M, Howard PM, Naughten ER. Ocular findings among patients with late‑diagnosed or poorly controlled homocystinuria compared with a screened, well controlled population. J AAPOS 2001;5:311‑5.
Access this article online Quick Response Code:
Website: www.ijo.in DOI: 10.4103/0301-4738.138637
Copyright of Indian Journal of Ophthalmology is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Indian Journal of Ophthalmology
Vol. 62 No. 7
case serves to remind us to consider massive sub‑retinal and suprachoroidal hemorrhages as causes of secondary angle closure glaucoma, especially in patients with known AMD and PCV.
ranibizumab treatment provided superior visual acuity (VA) gains compared to PDT. In addition, among the non‑randomized studies published in the literature, patients with myopic CNV treated using anti‑VEGF agents were reported to have better mean VA compared to patients treated with PDT.[4]
Wei Kiong Ngo1, Kai Xiong Cheong1, Colin SH Tan1,2
However, we would like to highlight that PDT may result in good visual outcomes in carefully selected patients, especially those with extrafoveal CNV lesions where the laser spot can be adjusted to spare the fovea. In a study of 24 eyes with myopic CNV,[5] we found that among patients who were treated with foveal‑sparing PDT, 77.8% achieved VA of ≥ 20/40, with a mean final logMAR VA of 0.26. An additional factor influencing the outcome is size of the myopic CNV lesion. Tan et al.[4] reported that myopic CNV lesions with a greatest linear diameter (GLD) of ≤ 1000 µm had better outcomes compared to those with larger GLD. While we acknowledge the difficulty of making direct comparisons of results from different studies, it is interesting to note that the visual outcomes in our study were comparable to, or in some cases better than, those reported from studies using anti‑VEGF agents.[5]
National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore 1
Correspondence to: Dr. Colin SH Tan, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11, Jalan Tan Tock Seng, Singapore ‑308433. E‑mail: [email protected]
References 1. Williams GS, Anderson L, Eddyshaw D. Macular hemorrhage as a cause of acute angle closure. Indian J Ophthalmol 2013;61:683‑4. 2. Lim TH, Laude A, Tan CS. Polypoidal choroidal vasculopathy: An angiographic discussion. Eye (Lond) 2010;24:483‑90. 3. Tan CS, Wong HT, Lim BA, Hee OK, Lim TH. Polypoidal choroidal vasculopathy causing massive suprachoroidal haemorrhage. Eye (Lond) 2007;21:132‑3. 4. Tan CS, Ngo WK, Lim LW, Cheong KX, Lim TH. Outcomes of polypoidal choroidal vasculopathy treated with ranibizumab monotherapy. Br J Ophthalmol 2013;97:1357‑8. 5. Koh A, Lee WK, Chen LJ, Chen SJ, Hashad Y, Kim H, et al. Everest study: Efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina 2012;32:1453‑64. Access this article online Quick Response Code:
Website: www.ijo.in DOI: 10.4103/0301-4738.138176
Anti‑VEGF agents are associated with systemic risks such as cerebrovascular accidents and other arterial thromboembolic events, especially for patients with pre‑existing disease.[5] In addition, intravitreal injections carry the risk of infectious endophthalmitis.[5] Some patients are unwilling to accept either the systemic or ocular risks associated with anti‑VEGF agents, and for them, PDT may be a valuable modality of treatment. In conclusion, ophthalmologists may wish to consider PDT in cases where the fovea can be spared, and where anti‑VEGF agents are unsuitable or unacceptable to patients. It has been shown that extrafoveal CNV lesions occur in between 18.5 and 32% of myopic CNV patients.[5] Therefore, we believe that PDT may still have a useful role in the management of myopic CNV, if patients are carefully selected.
Milton C Chew 1, Colin S Tan1,2 Department of Ophthalmology, Tan Tock Seng Hospital, 2Fundus Image Reading Center, National Healthcare Group Eye Institute, Singapore 1
Treatment options for myopic CNV ‑ Is photodynamic therapy still relevant? Dear Sir, We read with interest the article by Manayeth et al. [1] describing the use of low‑fluence photodynamic therapy (PDT) to successfully treat a patient who developed myopic choroidal neovascularization (CNV) following laser in situ Keratomileusis (LASIK), as well as the comment by Gopal[2] on the efficacy of anti‑vascular endothelial growth factor (anti‑VEGF) agents compared to PDT in the treatment of CNV. The Ranibizumab and PDT [verteporfin] evaluation in myopic choroidal neovascularization (RADIANCE) study,[3] a randomized controlled trial comparing ranibizumab against verteporfin PDT for the treatment of myopic CNV, reported that
Correspondence to: Dr. Colin S Tan, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11, Jalan Tan Tock Seng, Singapore - 308433. E‑mail: [email protected]
References 1. Manayath GJ, Narendran V, Ganesh A, Arora S. Low‑fluence photodynamic therapy for early onset choroidalneovascular membrane following laser in situ keratomileusis. Indian J Ophthalmol 2012;60:584‑5. 2. Santhan Gopal KS. Low‑fluence PDT better than anti‑vascular endothelial growth factor. Indian J Ophthalmol 2013;61:691. 3. Wolf S, Balciuniene VJ, Laganovska G, Menchini U, Ohno‑Matsui K, Sharma T, et al. RADIANCE study group. RADIANCE: A randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology 2014;121:682‑92.e2. 4. Tan CS, Chew MC, Lim KH, Lim TH. Factors affecting visual outcome of myopic choroidal neovascularization treated with
July 2014 Letters to the Editor verteporfin photodynamic therapy. Int J Ophthalmol 2013;6:327‑30. 5. Tan CS, Chew MC, Lim TH. Comparison of foveal‑sparing with foveal‑involving photodynamic therapy for myopic choroidal neovascularization. Eye (Lond) 2014;28:17‑22. Access this article online Quick Response Code:
Website: www.ijo.in DOI: 10.4103/0301-4738.138174
Varied phenotype of Homocystinuria: Possible diagnostic error Dear Sir, There are several crucial points to be made regarding the diagnostic criteria for the diagnosis of homocystinuria (HCU) due to cystathionine β‑synthase (CβS) in a recent article.[1] The authors have provided a comprehensive ophthalmological examination on the two siblings described. However, the diagnosis of HCU seemed to be based mainly on mildly elevated homocysteine levels (16.02 and 18µmol/L) and the ocular findings in the 2 cases, without concurrent levels of methionine, cystine, or other confirmatory tests. The presence of typical clinical signs may lead to a suspicion of CβS deficiency, but definitive diagnosis depends on a severely raised total homocysteine (tHcy; >100-400µmol/L) with low methionine and cystine levels. The confirmation of diagnosis is by CβS enzymology in cultured skin fibroblast and/or molecular analysis.[2] Plasma B12 and folate are routinely checked for nutritional deficiencies which can cause mildly elevated tHcy similar to the levels reported. Upon diagnosis, a trial of pyridoxine (B6) is given to ascertain clinical B6 responsiveness, as there is no correlation between in vitro and in vivo responsiveness.[3] Intellectual abilities as reported on sibling 1 as having developmental delay is at odds with a further statement which makes the assumption of probable “B6 responsive type” in the siblings based on the “mild systemic involvement and normal intelligence.” The authors further conclude that having developed ectopia lentis by 8 years as yet another factor for diagnosing HCU based on Mulvihill et al.[4] As a co‑author of the quoted article, the conclusion drawn by the authors on our study having shown that “ectopia lentis in homocystinuria develops after 1 year and maximum by 8 years” is incorrect. Instead, Mulvihill et al. documented that a diagnosis of HCU was made at a median age of 4 years (range: 1.2-8) in 10 out of 14 cases in the late detected group. A further four cases had a median age of diagnosis for HCU of 12.8 years (range: 4-23). All 14 cases had lens subuxation/dislocation at a median age of HCU diagnosis of 6 years (range: 1.25-28 years).[4] Our study only documented
835
the age at which time a diagnosis of HCU was made and did not determine when exactly ectopia lentis had occur.[4] Timing of ectopia lentis is not a diagnostic criteria. The authors correctly surmised that superonasal subluxation is atypical of HCU, however, the diagnosis of HCU in the reported cases has yet to be confirmed correctly. In view of the abdominal hernias and ectopia lentis, it would be usual to rule out other causes such as Marfan syndrome and to properly confirm the diagnosis of HCU. Vitamin deficiencies should be looked for as a cause of mild hyperhomocysteinemia. In the presence of second degree consanguinity, it may be useful to look for other causes of developmental delay, if indeed present in Sibling 1. In summary, the diagnosis of HCU must be confirmed and not simply based on mild hyperhomocysteinemia and some clinical features. Ascribing atypical features to HCU is premature especially when there is no evidence of the diagnosis being confirmed in a recognized manner.
Sufin Yap Department of Inherited Metabolic Diseases, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield S10 2TH, United Kingdom Correspondence to: Prof Dr Sufin Yap, Department of Inherited Metabolic Diseases, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield S10 2TH, United Kingdom. E‑mail: [email protected]
References 1. Kaliaperumal S, Kumar KP; Bhuvaneshwari. Varied phenotypic presentations of Homocystinuria in two siblings. Indian J Ophthalmol 2014;62:93‑4. 2. Mudd SH, Levy HL, Kraus JP. Disorders of transsulfuration. In: Scriver CR, Baeudet AL, Sly WS , Valle D, Childs B, Kinzler KW , et al. editors. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw‑Hill; 2001. p. 2007‑54. 3. Yap S, Naughten E. Homocystinuria due to cystathionine β‑synthase deficiency in Ireland: 25 years’ experience of a newborn screened and treated population with reference to clinical outcome and biochemical control. J Inher Metab Dis 1998;21:738‑47. Available from: http://dx.doi.org/10.1023/A: 1005445132327 [Last accessed on 2014 Mar 04]. 4. Mulvihill A, Yap S, O’Keefe M, Howard PM, Naughten ER. Ocular findings among patients with late‑diagnosed or poorly controlled homocystinuria compared with a screened, well controlled population. J AAPOS 2001;5:311‑5.
Access this article online Quick Response Code:
Website: www.ijo.in DOI: 10.4103/0301-4738.138637
Copyright of Indian Journal of Ophthalmology is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
