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Letters to the Editor In this, the first report of the new technique of LSS, we have demonstrated that loosening of scleral flap sutures can be achieved in a controlled, titratable manner. Indeed, we now deliberately restrict the on-table drainage in higher risk cases for hypotony and utilize LSS at 1–2 weeks post trabeculectomy to achieve the desired IOP in a manner analogous to delayed drainage in tube surgery.
Rohit Saxena FRCOphth, Marta Hovan MRCOphth and Stephen Vernon MD Department of Ophthalmology, Queens Medical Centre, Nottingham, UK Received 21 September 2014; accepted 28 September 2014.
REFERENCES 1. Lieberman MF. Suture lysis by laser and goniolens. Am J Ophthalmol 1983; 95: 257–8. 2. Schwartz AL, Weiss HS. Bleb leak with hypotony after laser suture lysis and trabeculectomy with mitomycin C. Arch Ophthalmol 1992; 110: 1049. 3. Tulay S, Mehmet C, Aygen B, Seda M, Orhan Z. Efficacy and complications of releasable suture trabeculectomy and standard trabeculectomy. Int Ophthalmol 2005; 26: 9–14.
391 visual acuity was 1/60 bilaterally. The left cornea was anaesthetic with intact conjunctival sensation. Despite standard management of the ocular surface disease, including topical antibiotics, topical steroids, topical lubricants, systemic tetracyclines, systemic azithromycin, in addition to the use of preservative-free medications, the large epithelial defect remained resistant to healing. The patient declined to have surgical intervention. In total, the neurotrophic defect was present for eight weeks. At her fifth clinic review, the topical neurotrophic growth factor, RGTA, was introduced. The patient inadvertently used RGTA four times a day during the first week, along with preservative-free chloramphenicol (bd) and Lacrilube (Allergan, Irvine, CA, USA) nocte. After one week of RGTA treatment, there was a significant reduction in the epithelial defect from measuring 9 mm × 7 mm (at largest horizontal and vertical dimensions) to 3 mm × 2.4 mm. Healing continued with complete closure of the defect by week three of RGTA treatment (Fig. 1). The cellular and molecular events involved in the healing response are complex. The early phases of healing are characterized by deposition of extra cellular matrix (ECM), and proliferation and migration of cells within this matrix, which act as a scaffold. Irrespective of the underlying cause, inflammation typically results in tissue destruc-
Novel matrix ReGeneraTing Agent promotes rapid corneal wound healing Corneal neurotrophic ulcers are among the most difficult ophthalmological conditions to treat. Elimination of toxic agents and use of preservative-free lubricants are often first-line treatments, but these currently available topical therapies may be insufficient in promoting the healing response. Other measures include the use of autologous serum, conjunctival flaps, tarsorrhaphy and amniotic membrane grafting.1 However, surgical techniques entail other risks, including central corneal scarring. A new matrix therapy agent (ReGeneraTing Agent [RGTA]; Cacicol20) has recently been introduced that provides a matrix to promote cell migration. This matrix also has a novel property of binding growth factors that additionally offer cues for migrating cells. We wish to report our successful initial experience with RGTA. Our patient inadvertently used more frequent dosing in the first week, and it is our observation that this resulted in a rapid healing response. An 81-year-old woman with a history of bilateral pseudophakia, chronic blepharitis, limbal stem cell deficiency and long-standing bilateral corneal and conjunctival scarring secondary to trachoma was referred with a large epithelial defect in her left eye. On examination her Competing/conflicts of interest: No stated conflict of interest. Funding sources: No stated funding sources.
Figure 1. Image showing initial neurotrophic epithelial defect and the weekly stages of healing following treatment with ReGeneraTing Agent (RGTA).
© 2014 Royal Australian and New Zealand College of Ophthalmologists
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392
Letters to the Editor
tion leading to ulceration and scarring. Pathological activity of proteolytic enzymes and active pro-inflammatory cytokines are implicated in the progression of tissue destruction. Heparan is a key ECM component, holding collagen fibrils together and providing binding sites for growth factors. Injury to tissues results in loss of heparan in the ECM and the bound growth factors. Polymers that mimic the binding action of heparan may offer a matrix for growth factors to bind and cue cell migration and proliferation. Tissue regenerating agents (RGTA) are designed to encourage healing by mimicking the action of destroyed heparan-sulphate molecules, thereby recreating a cellular environment in which cells can multiply and migrate. Application of RGTA has been demonstrated to accelerate the healing of skin ulcers.2 Clinical application of RGTA on corneal ulcers has also shown promising results, including in those ulcers resulting from post-infectious keratitis, chemical burns and neurotropic ulcers.3 Acute injury and the tissue remodeling both release lytic enzymes known as matrix metalloproteinases that degrade the ECM, initiating a negative repair–destruction cycle.4 RGTA may halt the progression of this breakdown cycle, improve collagen reorganization and have an antifibrotic action properties which are favourable in corneal wound healing. RGTA (Cacicol20) is supplied as a sterile single-dose solution of alpha 1–6 polycarboxymethyl glucose sulphate and penetrates into the cornea without crossing Descemet’s membrane. The frequency of application of this agent is yet to be determined. When all heparan-binding sites available in wound tissue are occupied by RGTA, excessive application may compete with heparan-binding growth factors. Heparan-bound growth factors/cytokines stored in the RGTA matrix could then be competitively removed, reducing healing efficacy. Based on this concept, the regimen of one drop every second day has been advocated, with daily or more frequently dosing of RGTA deemed to be inefficient.5 In our case, successful closure of the neurotrophic epithelial defect was observed within three weeks of RGTA treatment. The rapid healing response following inadvertent instillation of RGTA four times a day suggested that there may be additional mechanisms of action. Factors that propagate the negative repair–destruction loops are proinflammatory cytokines and free radicals. It is possible that excessive application of RGTA may remove these damaging cytokines from the ocular environment, thereby breaking the negative repair/destruction cycle, similar to a loading dose principle. While our case report provides further clinical evidence to suggest that RGTA may promote rapid healing, further in vitro studies and clinical trials are required to realise the full potentials of this novel agent.
Laura Hughes MB BCh, David Lockington FRCOphth, Sanjay Mantry FRCOphth and Kanna Ramaesh FRCOphth Tennent Institute of Ophthalmology, Gartnavel General Hospital, Glasgow, UK Received 30 September 2014; accepted 13 October 2014.
REFERENCES 1. Aifa A, Gueudry J, Portmann A, Delcampe A, Muraine M. Topical treatment with a new matrix therapy agent (RGTA) for the treatment of corneal neurotrophic ulcers. Invest Ophthalmol Vis Sci 2012; 53: 8181–5. 2. Groah SL, Libin A, Spungen M et al. Regenerating matrix-based therapy for chronic wound healing: a prospective within-subject pilot study. Int Wound J 2011; 8: 85–95. 3. Chebbi CK, Kichenin K, Amar N et al. Pilot study of a new matrix therapy agent (RGTA® OTR4120) in treatment-resistant corneal ulcers and corneal dystrophy. J Fr Ophtalmol 2008; 31: 465–71. 4. Wong TT, Daniels JT, Murphy G, Khaw PT. Matrix metalloproteinases in disease and repair processes in the anterior segment. Surv Ophthalmol 2002; 47: 239–56. 5. Pison A, Hay A, Dethorey G, Brezin A, Bourges J. Healing of a resistant corneal neurotrophic ulcer using a new matrix therapy agent (RGTA). Acta Ophthalmol 2013; 91: 0.
Social, infectious and environmental determinants of blindness in adult Aboriginal and Torres Strait Islander people and other Australian populations The overall standard of eye health of Indigenous people is substantially lower than other Australian populations, significantly the prevalence of blindness in Indigenous adults. Studies indicate that there are a number of interrelated determinants influencing the prevalence and severity of blindness, and these vary within the Indigenous communities, such as urban and rural Indigenous populations, as well as between these two groups.1 In 2008, the prevalence of blindness was 1.9% in Indigenous adults aged 40 years and over.2 When age standardized to the Australian population, the prevalence was 2.8% compared with 0.5% in other Australians.2–4 The relative risk of blindness in Indigenous adults was therefore around six times that of other Australians. Social determinants that influenced the incidence of blindness in Indigenous adults include education, employment, gender and standard of services such as housing, utilities, transport, communication, and the availability and quality of goods such as food, appliances, medicines, equipment and technology.5,6 With respect to blindness in Indigenous adults, infectious determinants relate solely to trachoma and include hygiene practices, mode of transmission and human, microbial and Competing/conflicts of interest: No stated conflict of interest. Funding sources: No stated funding sources.
© 2014 Royal Australian and New Zealand College of Ophthalmologists
Letters to the Editor In this, the first report of the new technique of LSS, we have demonstrated that loosening of scleral flap sutures can be achieved in a controlled, titratable manner. Indeed, we now deliberately restrict the on-table drainage in higher risk cases for hypotony and utilize LSS at 1–2 weeks post trabeculectomy to achieve the desired IOP in a manner analogous to delayed drainage in tube surgery.
Rohit Saxena FRCOphth, Marta Hovan MRCOphth and Stephen Vernon MD Department of Ophthalmology, Queens Medical Centre, Nottingham, UK Received 21 September 2014; accepted 28 September 2014.
REFERENCES 1. Lieberman MF. Suture lysis by laser and goniolens. Am J Ophthalmol 1983; 95: 257–8. 2. Schwartz AL, Weiss HS. Bleb leak with hypotony after laser suture lysis and trabeculectomy with mitomycin C. Arch Ophthalmol 1992; 110: 1049. 3. Tulay S, Mehmet C, Aygen B, Seda M, Orhan Z. Efficacy and complications of releasable suture trabeculectomy and standard trabeculectomy. Int Ophthalmol 2005; 26: 9–14.
391 visual acuity was 1/60 bilaterally. The left cornea was anaesthetic with intact conjunctival sensation. Despite standard management of the ocular surface disease, including topical antibiotics, topical steroids, topical lubricants, systemic tetracyclines, systemic azithromycin, in addition to the use of preservative-free medications, the large epithelial defect remained resistant to healing. The patient declined to have surgical intervention. In total, the neurotrophic defect was present for eight weeks. At her fifth clinic review, the topical neurotrophic growth factor, RGTA, was introduced. The patient inadvertently used RGTA four times a day during the first week, along with preservative-free chloramphenicol (bd) and Lacrilube (Allergan, Irvine, CA, USA) nocte. After one week of RGTA treatment, there was a significant reduction in the epithelial defect from measuring 9 mm × 7 mm (at largest horizontal and vertical dimensions) to 3 mm × 2.4 mm. Healing continued with complete closure of the defect by week three of RGTA treatment (Fig. 1). The cellular and molecular events involved in the healing response are complex. The early phases of healing are characterized by deposition of extra cellular matrix (ECM), and proliferation and migration of cells within this matrix, which act as a scaffold. Irrespective of the underlying cause, inflammation typically results in tissue destruc-
Novel matrix ReGeneraTing Agent promotes rapid corneal wound healing Corneal neurotrophic ulcers are among the most difficult ophthalmological conditions to treat. Elimination of toxic agents and use of preservative-free lubricants are often first-line treatments, but these currently available topical therapies may be insufficient in promoting the healing response. Other measures include the use of autologous serum, conjunctival flaps, tarsorrhaphy and amniotic membrane grafting.1 However, surgical techniques entail other risks, including central corneal scarring. A new matrix therapy agent (ReGeneraTing Agent [RGTA]; Cacicol20) has recently been introduced that provides a matrix to promote cell migration. This matrix also has a novel property of binding growth factors that additionally offer cues for migrating cells. We wish to report our successful initial experience with RGTA. Our patient inadvertently used more frequent dosing in the first week, and it is our observation that this resulted in a rapid healing response. An 81-year-old woman with a history of bilateral pseudophakia, chronic blepharitis, limbal stem cell deficiency and long-standing bilateral corneal and conjunctival scarring secondary to trachoma was referred with a large epithelial defect in her left eye. On examination her Competing/conflicts of interest: No stated conflict of interest. Funding sources: No stated funding sources.
Figure 1. Image showing initial neurotrophic epithelial defect and the weekly stages of healing following treatment with ReGeneraTing Agent (RGTA).
© 2014 Royal Australian and New Zealand College of Ophthalmologists
bs_bs_banner
392
Letters to the Editor
tion leading to ulceration and scarring. Pathological activity of proteolytic enzymes and active pro-inflammatory cytokines are implicated in the progression of tissue destruction. Heparan is a key ECM component, holding collagen fibrils together and providing binding sites for growth factors. Injury to tissues results in loss of heparan in the ECM and the bound growth factors. Polymers that mimic the binding action of heparan may offer a matrix for growth factors to bind and cue cell migration and proliferation. Tissue regenerating agents (RGTA) are designed to encourage healing by mimicking the action of destroyed heparan-sulphate molecules, thereby recreating a cellular environment in which cells can multiply and migrate. Application of RGTA has been demonstrated to accelerate the healing of skin ulcers.2 Clinical application of RGTA on corneal ulcers has also shown promising results, including in those ulcers resulting from post-infectious keratitis, chemical burns and neurotropic ulcers.3 Acute injury and the tissue remodeling both release lytic enzymes known as matrix metalloproteinases that degrade the ECM, initiating a negative repair–destruction cycle.4 RGTA may halt the progression of this breakdown cycle, improve collagen reorganization and have an antifibrotic action properties which are favourable in corneal wound healing. RGTA (Cacicol20) is supplied as a sterile single-dose solution of alpha 1–6 polycarboxymethyl glucose sulphate and penetrates into the cornea without crossing Descemet’s membrane. The frequency of application of this agent is yet to be determined. When all heparan-binding sites available in wound tissue are occupied by RGTA, excessive application may compete with heparan-binding growth factors. Heparan-bound growth factors/cytokines stored in the RGTA matrix could then be competitively removed, reducing healing efficacy. Based on this concept, the regimen of one drop every second day has been advocated, with daily or more frequently dosing of RGTA deemed to be inefficient.5 In our case, successful closure of the neurotrophic epithelial defect was observed within three weeks of RGTA treatment. The rapid healing response following inadvertent instillation of RGTA four times a day suggested that there may be additional mechanisms of action. Factors that propagate the negative repair–destruction loops are proinflammatory cytokines and free radicals. It is possible that excessive application of RGTA may remove these damaging cytokines from the ocular environment, thereby breaking the negative repair/destruction cycle, similar to a loading dose principle. While our case report provides further clinical evidence to suggest that RGTA may promote rapid healing, further in vitro studies and clinical trials are required to realise the full potentials of this novel agent.
Laura Hughes MB BCh, David Lockington FRCOphth, Sanjay Mantry FRCOphth and Kanna Ramaesh FRCOphth Tennent Institute of Ophthalmology, Gartnavel General Hospital, Glasgow, UK Received 30 September 2014; accepted 13 October 2014.
REFERENCES 1. Aifa A, Gueudry J, Portmann A, Delcampe A, Muraine M. Topical treatment with a new matrix therapy agent (RGTA) for the treatment of corneal neurotrophic ulcers. Invest Ophthalmol Vis Sci 2012; 53: 8181–5. 2. Groah SL, Libin A, Spungen M et al. Regenerating matrix-based therapy for chronic wound healing: a prospective within-subject pilot study. Int Wound J 2011; 8: 85–95. 3. Chebbi CK, Kichenin K, Amar N et al. Pilot study of a new matrix therapy agent (RGTA® OTR4120) in treatment-resistant corneal ulcers and corneal dystrophy. J Fr Ophtalmol 2008; 31: 465–71. 4. Wong TT, Daniels JT, Murphy G, Khaw PT. Matrix metalloproteinases in disease and repair processes in the anterior segment. Surv Ophthalmol 2002; 47: 239–56. 5. Pison A, Hay A, Dethorey G, Brezin A, Bourges J. Healing of a resistant corneal neurotrophic ulcer using a new matrix therapy agent (RGTA). Acta Ophthalmol 2013; 91: 0.
Social, infectious and environmental determinants of blindness in adult Aboriginal and Torres Strait Islander people and other Australian populations The overall standard of eye health of Indigenous people is substantially lower than other Australian populations, significantly the prevalence of blindness in Indigenous adults. Studies indicate that there are a number of interrelated determinants influencing the prevalence and severity of blindness, and these vary within the Indigenous communities, such as urban and rural Indigenous populations, as well as between these two groups.1 In 2008, the prevalence of blindness was 1.9% in Indigenous adults aged 40 years and over.2 When age standardized to the Australian population, the prevalence was 2.8% compared with 0.5% in other Australians.2–4 The relative risk of blindness in Indigenous adults was therefore around six times that of other Australians. Social determinants that influenced the incidence of blindness in Indigenous adults include education, employment, gender and standard of services such as housing, utilities, transport, communication, and the availability and quality of goods such as food, appliances, medicines, equipment and technology.5,6 With respect to blindness in Indigenous adults, infectious determinants relate solely to trachoma and include hygiene practices, mode of transmission and human, microbial and Competing/conflicts of interest: No stated conflict of interest. Funding sources: No stated funding sources.
© 2014 Royal Australian and New Zealand College of Ophthalmologists
