Acta Ophthalmologica 2015
and 0.1% SNJ-1656, respectively. Punctate keratitis was observed in 1 subject treated with 0.03% SNJ1656 and in 1 subject with 0.1% SNJ-1656. One subject had mild hepatic dysfunction after 0.05% SNJ1656 instillation. All adverse events were mild to moderate except in 1 case: hyperaemia in 1 subject treated with 0.03% SNJ-1656. Adverse events requiring treatment were headache and abdominal pain, conjunctival hyperaemia and nasopharyngitis in 1 subject each, all of which recovered. There was no abnormal value in haematologic and urine examinations, except in 1 subject for 0.05% SNJ-1656 with mild hepatic dysfunction, recovered after the cessation of SNJ-1656 without treatment. Systolic blood pressure was not different between day 0 and 7 in any of the groups before and after instillation except the placebo group before instillation, which were 131.6 20.2 and 126.3 18.7 mm Hg on day 0 and 7, respectively (p = 0.007).
Reference Tanihara H, Inatani M, Honjo M, Tokushige H, Azuma J & Araie M (2008): Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inhibitor, SNJ-1656, in healthy volunteers. Arch Ophthalmol 126: 309–315.
Correspondence: Hidenobu Tanihara, MD Department of Ophthalmology Faculty of Life Sciences Kumamoto University 1-1-1 Honjo, Chuo-Ku Kumamoto 860-8556, Japan Tel: +81 96 373 5247 Fax: +81 96 373 5249 Email: [email protected] The research was supported by Senju Pharmaceutical Co, Ltd, Osaka, Japan. Senju participated in the design of the study, conduct of the study, data collection, data management, data analysis, interpretation of the data, and preparation, review, and approval of the manuscript. HT1 has received consulting fees from Kowa, and MSD, and board membership fees from Senju Pharmaceutical, Santen Pharmaceutical, Alcon Japan, and Pfizer Japan. TI has no financial interest. HT2 is employee of Senju Pharmaceutical. MA has received consulting fees from Kowa, MSD, Topcon, and Allergan Japan, and board member-
ship fees from Senju Pharmaceutical, Santen Pharmaceutical, Alcon Japan, and Pfizer Japan and lecture fees from Carl Zeiss Japan, and has patents of Topcon. No company shown above writes or influences directly the wording of the manuscript.This research was supported by the National Natural Science Foundation of China (81371008), the Science and Technology Planning Project of Guangdong Province, China (No. 2012B031800353) and the Science and Research Project of Xiangnan University, China (No. 2013YJ67).
Relapse of acute lymphoblastic leukaemia (ALL) Nils A. Eide,1 Thomas P. Bærland,1 Ellen Sauesund,1 Jon Lømo,2 Marius LundIversen 2 and Sigurd Liestøl3 1
Department of Ophthalmology, Oslo University Hospital –HF and University of Oslo, Oslo, Norway; 2Department of Pathology, Oslo University Hospital – HF and University of Oslo, Oslo, Norway; 3Department of Haematology, Oslo University Hospital –HF and University of Oslo, Oslo, Norway doi: 10.1111/aos.12619
Editor, xtramedullary leukaemia remains an important complication of acute lymphoblastic leukaemia (ALL). Side-effects of treatment are observed more frequently than ocular infiltration of tumour cells (Sharma et al. (2004). The outcome for patients with ALL continues to improve with event-free survival (EFS) rates approaching 80% (Barredo et al. 2006). Involvement of the anterior segment is a rare (Patel et al. 2003; Sharma et al. 2004), but well documented manifestation, usually with a simultaneous relapse in the central nervous system. The prognosis for patients with isolated CNS recurrences is poor. It has been attempted to tailor the CNS radiation during intensified systemic therapy. The goal is to reduce the risk of long-term neurocognitive deficits and secondary brain neoplasms (Barredo et al. 2006). The aim of this letter was to stress the need for eye evaluation before stem cell transplantation (SCT) and the importance of new signs after SCT.
E
In March 2011, a 22-year-old man noticed weight loss and dyspnoea. In May 2011, enlarged lymph glands, hepatosplenomegaly and petechiae located on neck and lower extremities were detected. Abnormal values of leucocytes: 52 9 109/l, thrombocytes: 24 9 109/l, Hb: 8.3 g/dl and LD: 807 were measured. A maximal cell-rich bone marrow biopsy showed lymphoblast domination and flow cytometry revealed a B-lymphoblastic leukaemia, (83%) with the following immunophenotype: CD45+, CD34+, CD19+, CD20/+ (weak), CD10+ (strong) and Tdt+. Cytogenetic examination showed no abnormalities. Cerebrospinal fluid contained no blasts. A common B-cell ALL was diagnosed. Treatment according to the Hammersmith protocol was started. SCT was not indicated due to a good response to induction treatment with minimal residual disease. Episodes of uveitis in his left eye were treated by ophthalmologists at the University hospital and at the local eye department in the time between the primary treatment and a CNS relapse diagnosed in January 2013. Cerebrospinal fluid at this point was turbid and contained 165 blasts. Preconditioning prior to SCT was started with seven intrathecal methotrexate injections and radiotherapy to the CNS axis (given with 6 MeV photon beams, 10 doses of 1.8 Gy 5 days a week (total 18 Gy) to the brain and seven doses of 1.8 Gy 5 days a week (12.6 Gy) to the medullary cord, eyes not included) and hyper-CVAD block (cyclophosfamide, vincristine, antracycline and doxorubicin), which was given twice. In June 2013, allogenic SCT was performed with an unrelated, HLAcompatible female donor. Their blood groups were mismatched (donor A+, recipient B+). The result was good haematological reconstitution with >99% donor chimerism. In September 2013, an ocular relapse of was considered because of multiple, bilateral chorioretinal lesions (Fig. 1) and massive infiltration of iris in the left eye (Fig. 2). The eyes showed a poor response to intensive local steroid treatment. Magnetic resonance imaging (MRI) (orbital and cerebral), cerebrospinal fluid and BM-aspirate and BMbiopsy were normal. Pathology was documented using ultrasound biomicroscopy, wide-field fundus photographs
e395
Acta Ophthalmologica 2015
References
Fig. 1. Left: Segmentally thickened iris with prominent superficial vessels and colour shift from bluegrey to brown. Right: Multiple infiltrations in the posterior segment of the right eye involving the retina.
Barredo JC, Devidas M, Lauer SJ et al. (2006): Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a paediatric oncology group study. J Clin Oncol 24: 3142–3149. Patel SV, Herman DC, Anderson PM, Al-Zein NJ & Buettner H (2003): Iris and anterior chamber involvement in acute lymphoblastic leukemia. J Pediatr Hematology/Oncol 25: 653–656. Sharma T, Grewal J, Gupta S & Murray PI (2004): Ophthalmic manifestations of acute leukaemias: the ophthalmologist’s role. Eye 18: 663–672.
Correspondence: Nils Eide Eye Department Oslo University Hospital HF Postbox 4950 Nydalen N- 0424 Oslo, Norway Tel: +47 22118080 Fax: +47 22119989 Email: [email protected] Fig. 2. Ultrasound biomicroscopy. Abnormal iris in left eye, thickness 1.7 mm. (in the right eye iris measured 0.6 mm, not shown).
The need for toric intraocular lens implantation in public ophthalmology departments Christoffer Ostri, Lotte Falck, Gøril Boberg-Ans and Line Kessel
Fig. 3. Left: Leukaemic infiltration (haematoxylin–eosin) of the iris. Right: Small cells with scant cytoplasm, enlarged nuclei, nuclear membrane infolding and multiple nucleoli. The immunophenotype is CD45+, CD34+, CD38+, CD19+, CD20/low+, CD10 strong+ and Tdt+, identical with the immunophenotype found in the in bone marrow samples examined previously.
and biopsies from a hypopyon and iris lesion (Fig. 3). Microbial diagnostic vitreous tap was negative. A local ALL focus was confirmed with the same immunophenotype as shown previously. The process might represent an untreated focus of his ALL or a CNS relapse. The patient was treated with bilateral irradiation of the globes with 6 MeV photon beams, 15 doses of 2 Gy, 5 days a week (30 Gy) with normalization of anatomy and function. Both radiotherapy treatment plans were CT based (Figs 1–3). The prophylactic irradiation field excluded the eyes, despite his eye symptoms appearing after the initial
e396
leukaemia diagnosis. The eyes were likely affected prior to SCT. The risks of the eye biopsies were acceptable. Until now, there has been no ocular relapse. Unfortunately, a systemic recurrence was diagnosed by BM biopsy in March 2014 and chemotherapy was started. The prognosis for patients with CNS relapse is uncertain. Four year EFS is 77% overall, 49% in high risk groups (Barredo et al. 2006). The authors would like to stress the need for eye evaluations before SCT, preconditioning with irradiation of the orbit if ‘uveitis’ appears before a CNS relapse and the importance of reacting to new ocular signs after SCT.
Department of Ophthalmology, Glostrup University Hospital, Copenhagen, Denmark doi: 10.1111/aos.12584
Editor, stigmatism is often present in patients undergoing cataract surgery. Implanting toric intra-ocular lenses (IOL) is a safe way to increase the chance of spectacle independence after cataract surgery (Holland et al. 2010); however, toric IOL0 s cost more than conventional IOL0 s, and in many public ophthalmology departments, toric IOL0 s are simply not offered to patients, unless the preoperative corneal astigmatism (PCA) is very high. We experience an increasing patient demand for surgical astigmatism correction in the setting of an upcoming cataract surgery, in particular among
A
and 0.1% SNJ-1656, respectively. Punctate keratitis was observed in 1 subject treated with 0.03% SNJ1656 and in 1 subject with 0.1% SNJ-1656. One subject had mild hepatic dysfunction after 0.05% SNJ1656 instillation. All adverse events were mild to moderate except in 1 case: hyperaemia in 1 subject treated with 0.03% SNJ-1656. Adverse events requiring treatment were headache and abdominal pain, conjunctival hyperaemia and nasopharyngitis in 1 subject each, all of which recovered. There was no abnormal value in haematologic and urine examinations, except in 1 subject for 0.05% SNJ-1656 with mild hepatic dysfunction, recovered after the cessation of SNJ-1656 without treatment. Systolic blood pressure was not different between day 0 and 7 in any of the groups before and after instillation except the placebo group before instillation, which were 131.6 20.2 and 126.3 18.7 mm Hg on day 0 and 7, respectively (p = 0.007).
Reference Tanihara H, Inatani M, Honjo M, Tokushige H, Azuma J & Araie M (2008): Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inhibitor, SNJ-1656, in healthy volunteers. Arch Ophthalmol 126: 309–315.
Correspondence: Hidenobu Tanihara, MD Department of Ophthalmology Faculty of Life Sciences Kumamoto University 1-1-1 Honjo, Chuo-Ku Kumamoto 860-8556, Japan Tel: +81 96 373 5247 Fax: +81 96 373 5249 Email: [email protected] The research was supported by Senju Pharmaceutical Co, Ltd, Osaka, Japan. Senju participated in the design of the study, conduct of the study, data collection, data management, data analysis, interpretation of the data, and preparation, review, and approval of the manuscript. HT1 has received consulting fees from Kowa, and MSD, and board membership fees from Senju Pharmaceutical, Santen Pharmaceutical, Alcon Japan, and Pfizer Japan. TI has no financial interest. HT2 is employee of Senju Pharmaceutical. MA has received consulting fees from Kowa, MSD, Topcon, and Allergan Japan, and board member-
ship fees from Senju Pharmaceutical, Santen Pharmaceutical, Alcon Japan, and Pfizer Japan and lecture fees from Carl Zeiss Japan, and has patents of Topcon. No company shown above writes or influences directly the wording of the manuscript.This research was supported by the National Natural Science Foundation of China (81371008), the Science and Technology Planning Project of Guangdong Province, China (No. 2012B031800353) and the Science and Research Project of Xiangnan University, China (No. 2013YJ67).
Relapse of acute lymphoblastic leukaemia (ALL) Nils A. Eide,1 Thomas P. Bærland,1 Ellen Sauesund,1 Jon Lømo,2 Marius LundIversen 2 and Sigurd Liestøl3 1
Department of Ophthalmology, Oslo University Hospital –HF and University of Oslo, Oslo, Norway; 2Department of Pathology, Oslo University Hospital – HF and University of Oslo, Oslo, Norway; 3Department of Haematology, Oslo University Hospital –HF and University of Oslo, Oslo, Norway doi: 10.1111/aos.12619
Editor, xtramedullary leukaemia remains an important complication of acute lymphoblastic leukaemia (ALL). Side-effects of treatment are observed more frequently than ocular infiltration of tumour cells (Sharma et al. (2004). The outcome for patients with ALL continues to improve with event-free survival (EFS) rates approaching 80% (Barredo et al. 2006). Involvement of the anterior segment is a rare (Patel et al. 2003; Sharma et al. 2004), but well documented manifestation, usually with a simultaneous relapse in the central nervous system. The prognosis for patients with isolated CNS recurrences is poor. It has been attempted to tailor the CNS radiation during intensified systemic therapy. The goal is to reduce the risk of long-term neurocognitive deficits and secondary brain neoplasms (Barredo et al. 2006). The aim of this letter was to stress the need for eye evaluation before stem cell transplantation (SCT) and the importance of new signs after SCT.
E
In March 2011, a 22-year-old man noticed weight loss and dyspnoea. In May 2011, enlarged lymph glands, hepatosplenomegaly and petechiae located on neck and lower extremities were detected. Abnormal values of leucocytes: 52 9 109/l, thrombocytes: 24 9 109/l, Hb: 8.3 g/dl and LD: 807 were measured. A maximal cell-rich bone marrow biopsy showed lymphoblast domination and flow cytometry revealed a B-lymphoblastic leukaemia, (83%) with the following immunophenotype: CD45+, CD34+, CD19+, CD20/+ (weak), CD10+ (strong) and Tdt+. Cytogenetic examination showed no abnormalities. Cerebrospinal fluid contained no blasts. A common B-cell ALL was diagnosed. Treatment according to the Hammersmith protocol was started. SCT was not indicated due to a good response to induction treatment with minimal residual disease. Episodes of uveitis in his left eye were treated by ophthalmologists at the University hospital and at the local eye department in the time between the primary treatment and a CNS relapse diagnosed in January 2013. Cerebrospinal fluid at this point was turbid and contained 165 blasts. Preconditioning prior to SCT was started with seven intrathecal methotrexate injections and radiotherapy to the CNS axis (given with 6 MeV photon beams, 10 doses of 1.8 Gy 5 days a week (total 18 Gy) to the brain and seven doses of 1.8 Gy 5 days a week (12.6 Gy) to the medullary cord, eyes not included) and hyper-CVAD block (cyclophosfamide, vincristine, antracycline and doxorubicin), which was given twice. In June 2013, allogenic SCT was performed with an unrelated, HLAcompatible female donor. Their blood groups were mismatched (donor A+, recipient B+). The result was good haematological reconstitution with >99% donor chimerism. In September 2013, an ocular relapse of was considered because of multiple, bilateral chorioretinal lesions (Fig. 1) and massive infiltration of iris in the left eye (Fig. 2). The eyes showed a poor response to intensive local steroid treatment. Magnetic resonance imaging (MRI) (orbital and cerebral), cerebrospinal fluid and BM-aspirate and BMbiopsy were normal. Pathology was documented using ultrasound biomicroscopy, wide-field fundus photographs
e395
Acta Ophthalmologica 2015
References
Fig. 1. Left: Segmentally thickened iris with prominent superficial vessels and colour shift from bluegrey to brown. Right: Multiple infiltrations in the posterior segment of the right eye involving the retina.
Barredo JC, Devidas M, Lauer SJ et al. (2006): Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: a paediatric oncology group study. J Clin Oncol 24: 3142–3149. Patel SV, Herman DC, Anderson PM, Al-Zein NJ & Buettner H (2003): Iris and anterior chamber involvement in acute lymphoblastic leukemia. J Pediatr Hematology/Oncol 25: 653–656. Sharma T, Grewal J, Gupta S & Murray PI (2004): Ophthalmic manifestations of acute leukaemias: the ophthalmologist’s role. Eye 18: 663–672.
Correspondence: Nils Eide Eye Department Oslo University Hospital HF Postbox 4950 Nydalen N- 0424 Oslo, Norway Tel: +47 22118080 Fax: +47 22119989 Email: [email protected] Fig. 2. Ultrasound biomicroscopy. Abnormal iris in left eye, thickness 1.7 mm. (in the right eye iris measured 0.6 mm, not shown).
The need for toric intraocular lens implantation in public ophthalmology departments Christoffer Ostri, Lotte Falck, Gøril Boberg-Ans and Line Kessel
Fig. 3. Left: Leukaemic infiltration (haematoxylin–eosin) of the iris. Right: Small cells with scant cytoplasm, enlarged nuclei, nuclear membrane infolding and multiple nucleoli. The immunophenotype is CD45+, CD34+, CD38+, CD19+, CD20/low+, CD10 strong+ and Tdt+, identical with the immunophenotype found in the in bone marrow samples examined previously.
and biopsies from a hypopyon and iris lesion (Fig. 3). Microbial diagnostic vitreous tap was negative. A local ALL focus was confirmed with the same immunophenotype as shown previously. The process might represent an untreated focus of his ALL or a CNS relapse. The patient was treated with bilateral irradiation of the globes with 6 MeV photon beams, 15 doses of 2 Gy, 5 days a week (30 Gy) with normalization of anatomy and function. Both radiotherapy treatment plans were CT based (Figs 1–3). The prophylactic irradiation field excluded the eyes, despite his eye symptoms appearing after the initial
e396
leukaemia diagnosis. The eyes were likely affected prior to SCT. The risks of the eye biopsies were acceptable. Until now, there has been no ocular relapse. Unfortunately, a systemic recurrence was diagnosed by BM biopsy in March 2014 and chemotherapy was started. The prognosis for patients with CNS relapse is uncertain. Four year EFS is 77% overall, 49% in high risk groups (Barredo et al. 2006). The authors would like to stress the need for eye evaluations before SCT, preconditioning with irradiation of the orbit if ‘uveitis’ appears before a CNS relapse and the importance of reacting to new ocular signs after SCT.
Department of Ophthalmology, Glostrup University Hospital, Copenhagen, Denmark doi: 10.1111/aos.12584
Editor, stigmatism is often present in patients undergoing cataract surgery. Implanting toric intra-ocular lenses (IOL) is a safe way to increase the chance of spectacle independence after cataract surgery (Holland et al. 2010); however, toric IOL0 s cost more than conventional IOL0 s, and in many public ophthalmology departments, toric IOL0 s are simply not offered to patients, unless the preoperative corneal astigmatism (PCA) is very high. We experience an increasing patient demand for surgical astigmatism correction in the setting of an upcoming cataract surgery, in particular among
A
