- Email: [email protected]
Neurotrophic keratitis after transscleral diode laser cyclophotocoagulation
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ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Original article
Neurotrophic keratitis after transscleral diode laser cyclophotocoagulation夽,夽夽 Á. Fernández-Vega González a,b,∗ , R.I. Barraquer Compte a,b , A.L. Cárcamo Martínez b , M. Torrico Delgadillo b , M.F. de la Paz a,b a b
Centro de Oftalmología Barraquer, Barcelona, Spain Institut Universitari Barraquer, Universidad Autónoma de Barcelona, Barcelona, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history:
Objective: To study the relationship between treatment with diode laser transscleral
Received 25 May 2015
cyclophotocoagulation and development a neurotrophic keratitis due to the damage of the
Accepted 1 December 2015
sensitive corneal innervation.
Available online xxx
Methods: A study was conducted on 5 eyes of 5 patients who were treated with diode laser transscleral cyclophotocoagulation and soon developed neurotrophic ulcers. Personal char-
Keywords:
acteristics of the patients were collected, as well as refraction and risk factors for corneal
Neurotrophic keratitis
hypoesthesia, and the parameters of the laser used in the surgery.
Transscleral cyclophotocoagulation
Results: It was found that the 5 patients had predisposing factors of corneal hypoesthesia
Neurotrophic corneal ulcer
prior to surgery (chronic use of topical beta blockers, surgery with corneal incisions, diabetes mellitus, or corneal dystrophies); however none had developed neurotrophic keratitis until the cyclophotocoagulation was performed. It also showed that 4 of them were highly myopic, and they all were treated with high laser parameters (with an average of 2880 mW for 3 s at an average surface of 275◦ ), triggering neurotrophic ulcers between 10 and 35 days after surgery. Conclusion: Neurotrophic keratitis is a rare complication that can occur after diode laser transscleral cyclophotocoagulation, secondary to the damage of the long ciliary nerves. The emergence of this disorder can be triggered by the existence of previous risk factors, including high myopia, thus it is important to respect the recommended treatment parameters to prevent the development of this disorder. ˜ © 2015 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
夽 Please cite this article as: Fernández-Vega González Á, Barraquer Compte RI, Cárcamo Martínez AL, Torrico Delgadillo M, de la Paz MF. Queratitis neurotrófica posciclofotocoagulación transescleral con láser diodo. Arch Soc Esp Oftalmol. 2016. http://dx.doi.org/10.1016/j.oftal.2015.12.001 夽夽 Partially presented in the Master’s Degree in Corneal and Ocular Surface Pathology at the Autonomous University of Barcelona and Barraquer University Institute and the Congress of the Catalan Society of Ophthalmology, Barcelona, November 2015. ∗ Corresponding author. E-mail address: [email protected] (Á. Fernández-Vega González). ˜ 2173-5794/© 2015 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
OFTALE-924; No. of Pages 7
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Queratitis neurotrófica posciclofotocoagulación transescleral con láser diodo r e s u m e n Palabras clave:
Objetivo: Estudiar la relación existente entre el tratamiento con ciclofotocoagulación trans-
Queratitis neurotrófica
escleral con láser de diodo y el desarrollo de queratitis neurotróficas por lesión de la
Ciclofotocoagulación
inervación sensitiva corneal.
transescleral
Métodos: Se han estudiado 5 ojos de 5 pacientes que fueron tratados con ciclofotocoagulación
Úlcera corneal neurotrófica
transescleral con láser de diodo y al poco tiempo desarrollaron úlceras neurotróficas. Se han recogido las diferentes características personales de los pacientes, incluyendo refracción y factores de riesgo de hipoestesia corneal, así como los parámetros de láser empleados en el tratamiento. Resultados:
Se comprobó que los 5 pacientes presentaban factores predisponentes de
hipoestesia corneal previos a la cirugía (uso de betabloqueantes tópicos crónicos, cirugías corneales, diabetes mellitus o distrofias corneales). Sin embargo, ninguno había desarrollado queratitis neurotróficas hasta el momento de la ciclofotocoagulación. Se evidenció, además, que 4 de ellos eran altos miopes y que todos ellos fueron tratados con parámetros elevados de láser (2.880 mW por 3 s, en una superficie de 275◦ de media), y se desencadenaron úlceras neurotróficas entre los 10 y los 35 días después de la cirugía. Conclusiones: La queratopatía neurotrófica es una complicación poco frecuente que puede aparecer tras la ciclofotocoagulación transescleral con láser de diodo, debido a la lesión secundaria de los nervios ciliares largos. La aparición de esta se puede ver favorecida por la existencia de factores de riesgo previos, entre los que hay que incluir la alta miopía. Es crucial respetar los parámetros de tratamiento recomendados, para evitar la aparición de esta dolencia. ˜ de Oftalmología. Publicado por Elsevier España, S.L.U. Todos © 2015 Sociedad Espanola los derechos reservados.
Introduction The cornea is one of the most densely innervated tissues in the human body. Innervation is mainly by the ophthalmic division of the trigeminal nerve which, through the long ciliary nerves, exerts a trophic influence on the corneal epithelium.1–5 Alteration of this sensory innervation can lead to loss of that trophic influence, causing a deficiency in the blink and tear reflexes, a reduction in cell metabolism and decreased proliferation of basal cells, which can result in epithelial defects and affect the healing of the cornea. All this can lead to neurotrophic keratitis, with the development of recurrent and difficult-to-treat corneal ulcers.6–9 The most common cause is herpes simplex or herpes zoster virus eye infection, but any illness, surgical or traumatic procedure that damages corneal sensory innervation can lead to neurotrophic keratitis.6,10–14 Diode-laser transscleral cyclophotocoagulation is a method used to reduce intraocular pressure (IOP) in patients with glaucoma which destroys the secretory ciliary epithelial cells, thereby reducing the secretion of aqueous humour. The radiation produced by the diode laser interacts with the target biological tissues and causes a photothermal effect which generates photocoagulation, necrosis and inflammation of the tissues.15–20 Although treatment in each case has to be individualised, when performing transscleral cyclophotocoagulation using a continuous wavelength semiconductor laser diode that emits a wavelength of 810 nm, it is recommended that the contact probe be placed 1–1.5 mm posterior to the
limbus with no more than 24 hits in an area of 170◦ –270◦ . Moreover, it is advisable to use powers of 1500–2500 mW for 1.5–2.5 s (2.25–6.25 J), avoiding the 3- and 9-o’clock meridians as far as possible in order not to damage the vessels and long ciliary nerves. A standard technique would be to start using low powers of around 1500 mW for 1.5 s (2.25 J), and then gradually increase until an audible “pop” sound is heard, indicating thermal decomposition of the tissues, then lower the power. However, it is recommended not to exceed 2500 mW for 2.5 s (6.25 J) as the chances of complications increase.15–17,21–26 The complications of this treatment published so far include anterior uveitis, eye pain, temporary increase in IOP, choroidal detachment, chronic hypotonia, decompensated corneal graft, macular pucker, cystoid macular oedema, hyphema, vitreous haemorrhage, loss of visual acuity, retinal detachment, conjunctival and scleral burns, corneal oedema, sympathetic ophthalmia and phthisis bulbi.15–17,27 There is very little literature on the relationship between transscleral diode laser cyclophotocoagulation and neurotrophic keratitis,28,29 so the possible role of this technique in the development of neurotrophic ulcers is not fully understood.
Subjects, materials and methods This article presents the retrospective descriptive case series study in which we reviewed patients with glaucoma at the
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Fig. 1 – Patient 1. 2.5 mm × 1.5 mm neurotrophic corneal ulcer stained with fluorescein 17 days after cyclophotocoagulation.
Barraquer Ophthalmology Centre who were treated with transscleral cyclophotocoagulation and shortly thereafter developed neurotrophic keratitis. We found 5 eyes in 5 patients who developed neurotrophic ulcers soon after cyclodestructive treatment and studied their different personal characteristics, including gender, age, type of glaucoma, refraction, previous medical and surgical history and previous medical treatments, as well as risk factors for corneal hypoaesthesia. The laser parameters used to perform the cyclophotocoagulation were recorded, with the number of hits made, the extent of the area treated in degrees and the power used. The surgical technique performed on all the patients included in the study was transscleral cyclophotocoagulation with continuous-wave semiconductor laser diode emitting at 810 nm. The laser system used was an Iris Medical Oculight SL® by IRIDEX with a G-Probe TM. We determined the time from surgery until onset of neurotrophic defects and the treatment received and outcome. Two of the patients included in the study had died and the other 3 continued under follow-up at our centre.
3
Fig. 2 – Patient 1. Resolution of neurotrophic corneal ulcer one and a half months later, with positive fluorescein closure line.
Fig. 3 – Patient 2. 6 mm × 3 mm neurotrophic corneal ulcer stained with fluorescein 18 days after cyclophotocoagulation.
Results The study included 5 patients, 3 male and 2 female, with a mean age of 63.2 years. All 5 had chronic open-angle glaucoma and had been under follow-up for an average of 12.2 years prior to the cyclophotocoagulation treatment. During that time, they were all treated long-term with beta-blockers, prostaglandins and at least one other topical hypotensive agent (an alpha-agonist or a carbonic anhydrase inhibitor). In 2 cases, filtering surgery was required to control their IOP (one required 2 trabeculectomies 6 and 3 years before the cyclophotocoagulation (Figs. 1 and 2) and the other had an Ahmed valve implanted 3 years beforehand). Only 1 of the patients (Figs. 3 and 4) had not previously had surgery on the eye on which the cyclodestructive procedure was applied. In the other cases, in addition to the filtering surgery already mentioned, 3 patients had undergone
Fig. 4 – Patient 2. Corneal erosion of 0.5 mm, one and a half months after onset.
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Fig. 5 – Patient 3. Residual corneal leucoma after neurotrophic corneal ulcer.
extracapsular cataract extraction (10, 27 and 36 years before the cyclodestructive treatment), and one had also required penetrating keratoplasty twice (first for bullous keratopathy and then for fungal keratitis), the second of which was a year before the cyclophotocoagulation (Fig. 5). One of the cases also had corneal dystrophy, diagnosed 30 years previously, but which had not caused any symptoms in all that time. Another important finding was that 3 of the patients had high myopia with a mean spherical equivalent of −7.3 diopters (D). The refraction was not available for the other 2 patients, but for one of them, who had Down’s syndrome, we did have the biometry measurement (Figs. 6 and 7), 24.98 mm, which indicated axial myopia. In terms of general previous medical history, one of the patients had been diagnosed with type 2 diabetes 3 years previously, although there had been no eye involvement up to the time of treatment (Figs. 8 and 9). Focusing on the laser parameters used during cyclophotocoagulation, we found that the mean number of hits was 22.4 on an average surface area of 274◦ (with a range of 200–360◦ ). The mean energy used in these cases was 2880 mW for 3 s
Fig. 6 – Patient 4. Vascularised residual leucoma after multiple neurotrophic keratitis.
Fig. 7 – Patient 4. Phthisis bulbi.
(8.6 J) with a range of 7.5–9 J; 3 patients received hits over 270◦ or more, with 3000 mW for 3 s (9 J) (Table 1). After the cyclophotocoagulation all the patients developed neurotrophic keratitis, with the first epithelial defects appearing, on average, 22 days (range 10–35 days) posttreatment. In all cases, the ulcers were treated with topical artificial tears, topical antibiotics and therapeutic contact lens or eyepatch. Four of the patients also required blood components (50% autologous serum or platelet-rich plasma) and one was also treated with minoarte (carboxymethyl glucose sulfate). The neurotrophic defects took an average of 36 days to clear up. All the patients had further episodes of recurrent corneal ulcers which, in 3 cases, resulted in residual leucoma affecting visual acuity. The Down’s syndrome patient’s eye was the one with the worst prognosis, although not because of neurotrophic keratitis, but because he suffered total retinal detachment that led to phthisis bulbi. Two of the patients required a second cyclophotocoagulation session due to poor control of their IOP and, once again, high parameters were used (average of 17.5 hits over an area
Fig. 8 – Patient 5. 6 mm × 4.5 mm neurotrophic corneal ulcer stained with fluorescein, one month after cyclophotocoagulation.
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Table 1 – Characteristics of the study patients and laser parameters used. Patient
Gender
Age
Corneal hypoaesthesia RF
1 2 3 4 5 Mean
Female Male Male Male Female
74 64 78 29 71 63.2
BB, Trabeculectomy BB BB, ECCE, PK BB, ECCE BB, ECCE, corneal dystrophy, DM2
No. of hits 26 20 11 30 25 22.4
Degrees
Potency (mW)
270 270 200 270 360 274
2900 3000 3000 3000 2500 2880
Duration (s) 3 3 3 3 3 3
T◦ onset (days) 17 18 10 35 30 22
BB, beta-blockers; DM2, type 2 diabetes mellitus; ECCE, extracapsular cataract extraction; RF, risk factors; PK, penetrating keratoplasty; T◦ onset, time neurotrophic ulcers appeared.
Fig. 9 – Patient 5. Residual leucoma after resolution of the condition one month after onset.
of 195◦ and mean power of 2925 mW for 3 s). Again, in the following month, both patients developed neurotrophic corneal defects which continued to recur over the next few years.
Discussion The aim of this study was to analyse the relationship between treatment with diode laser transscleral cyclophotocoagulation and development of neurotrophic keratitis. It is well known that long-term use of topical beta-blockers, corneal surgery with large incisions, diabetes mellitus and some corneal dystrophies are predisposing and trigger factors for corneal hypoaesthesia.16,30 In our series, we found that 2 patients had one of these risk factors (long-term topical instillation of beta-blockers), 2 patients had 2 (long-term topical instillation of beta-blockers and eye surgery with large corneal incisions – ECCE and penetrating keratoplasty) and the fifth patient had 4 (long-term topical beta-blockers, ECCE, diabetes mellitus and corneal dystrophy). However, they had all had been living with these risk factors for years without developing neurotrophic keratitis, until they had cyclophotocoagulation. Even the patient who had undergone 2 keratoplasties and an ECCE, who was the one with the shortest free interval between the risk factor and the cyclophotocoagulation, went a year after the last transplant without any neurotrophic damage. We would
therefore argue that these factors may have been predisposing factors, but they were not what triggered the neurotrophic keratitis. The trigger in our patients was the transscleral cyclophotocoagulation which, due to the application of high laser power (8.6 J on average) over a large area (270–360◦ ), when added to the predisposing factors, caused damage to the long ciliary nerves and resulted in neurotrophic keratopathy. As has been demonstrated, if radiation is applied for longer than recommended, heat conduction can cause raising of the temperature beyond the irradiated target tissue, indirectly causing undesired effects in adjacent non-target regions. Add to that the application of a high average power level, and we create a very harmful vaporisation effect, in which the tissue temperature increases and mechanical rupture and thermal decomposition of tissues occur, the sign of which is the audible “pop” we mentioned earlier.20,22,23,25,26 This situation requires lower laser power as described in the application technique. In the study by Schuman et al.26 in 1991, the effect of transscleral cyclophotocoagulation was analysed on human cadaver eyes using different energy levels. The authors concluded that, above 5 J, explosive tissue damage occurs and that the optimum power setting for diode laser cyclophotocoagulation is between 3 and 4.5 J. As discussed earlier, most experts recommend not exceeding 2500 mW for 2.5 s (6.25 J) and not treating an area greater than 270◦ , as doing otherwise can increase the risk of complications.15–17,21–24,26 However, in our study, the mean energy used (2880 mW for 3 s [8.6 J over 274◦ ]) was considerably higher than the figure recommended. In an experimental model with 6 mice subjected to stereotactic trigeminal electrolysis,14 the corneal nerves were not histologically recognisable at 48 h. In that study, over the following 7 days, a reduction in basal epithelial cell proliferation was observed with increase in cell apoptosis in all the layers of the cornea. In our patients, the diode laser damaged the sensory nerve fibres, with the result that the undamaged innervation remaining in the areas not irradiated with the laser was not enough to maintain the epithelium, and they all developed neurotrophic keratitis over the following 10–35 days. Histology studies would be required to determine the extent of the damage to corneal innervation and be able to demonstrate the damage to the long ciliary nerves after the cyclophotocoagulation, but we believe the most plausible explanation to be that the damage was caused by a hyperthermia lesion due to the excessive energy levels used in the treatment.
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Another finding we consider relevant is that 4 of the patients had high myopia (spherical equivalent −7.3 D). This is important, since people with high myopia have thinner sclera than normal, which means that the long ciliary nerves, which in the ciliary body run through the suprachoroids and, as they approach the limbus, become integrated into the sclera,1–5 are more likely to be damaged by transscleral cyclophotocoagulation. In 1997, Palmer et al. showed in their experiment31 that differences in scleral thickness must be taken into account in the energy to be used with cyclophotocoagulation, since patients with thinner sclera are more likely to suffer greater tissue damage. Accordingly, high myopia must also be taken into account, as it may act as an additional risk factor. We were able to conclude that neurotrophic keratopathy is a rare complication that can occur after laser diode transscleral cyclophotocoagulation as a result of damage to the long ciliary nerves. It may be more likely in patients who already have risk factors prior to the treatment, such as the use of topical beta-blockers, previous eye surgery, diabetes mellitus, corneal dystrophies and high myopia. To avoid complications with this technique, it is crucial to respect the recommended treatment parameters. Particular care should above all be taken with patients who have the above risk factors, and we recommend using lower parameters in terms of area and power. If neurotrophic keratitis develops, blood components and carboxymethyl glucose sulfate can be helpful for resolving the disorder.
Conflict of interest The authors have no commercial interests and have received no financial support.
references
1. Shaheen BS, Bakir M, Jain S. Corneal nerves in health and disease: a review. Surv Ophthalmol. 2014;59:263–85. 2. Parissi M, Karanis G, Randjelovic S, Germundsson J, Poletti E, Ruggeri A, et al. Standardized baseline human corneal subbasal nerve density for clinical investigations with laser-scanning in vivo confocal microscopy. Invest Ophthalmol Vis Sci. 2013;54:7091–102. 3. Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the human corneal innervation. Exp Eye Res. 2010;90:478–92. 4. Patel DV, McGhee CN. In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review. Br J Ophthalmol. 2009;93:853–60. 5. Müller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76:521–42. 6. Bernard H, Chang S, Erich B, Groos J Jr. Neurotrophic keratitis. In: Krachmer JH, Mannis MJ, Holland EJ, editors. Cornea: fundamentals diagnosis and management. Mosby Elsevier; 2011. p. 1101–10. 7. Semeraro F, Forbice E, Romano V, Angi M, Romano MR, Filippelli ME, et al. Neurotrophic keratitis. Ophthalmologica. 2014;231:191–7. 8. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571–9. 9. Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17:989–95.
10. Chucair-Elliott AJ, Zheng M, Carr DJ. Degeneration and regeneration of corneal nerves in response to HSV-1 infection. Invest Ophthalmol Vis Sci. 2015;56:1097–107. 11. Gallar J, Tervo TM, Neira W, Holopainen JM, Lamberg ME, ˜ Minana F. Selective changes in human corneal sensation associated with herpes simplex virus keratitis. Invest Ophthalmol Vis Sci. 2010;51:4516–22. 12. Hamrah P, Cruzat A, Dastjerdi MH, Zheng L, Shahatit BM, Bayhan HA, et al. Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology. 2010;117:1930–6. 13. Lambiase A, Sacchetti M, Mastropasqua A, Bonini S. Corneal changes in neurosurgically induced neurotrophic keratitis. JAMA Ophthalmol. 2013;131:1547–53. 14. Ferrari G, Chauhan SK, Ueno H, Nallasamy N, Gandolfi S, Borges L, et al. A novel mouse model for neurotrophic keratopathy: trigeminal nerve stereotactic electrolysis through the brain. Invest Ophthalmol Vis Sci. 2011;52:2532–9. 15. Kanski J, Bowling B. Glaucoma. In: Kanski J, Bowling B, editors. ˜ Oftalmología clínica. 7th edition Barcelona: Elsevier Espana, S.L.; 2012. p. 390. 16. Lanzagorta A, Gutierrez E. Procedimientos ciclodestructivos. In: Urcelay JL, editor. Cirugía de glaucoma paso a paso, 11. Barcelona: Glosa SL; 2012. p. 119–22. 17. Bhartiya S, Ichhpijani P, Angmo D. Transscleral diode cyclophotocoagulation. In: Shaarawy T, Dada T, Bhartiya S, editors. Glaucoma surgery: textbook of the International Society of Glaucoma Surgery. New Delhi: Jaype Brother Medical Publisher; 2014. p. 65–70. 18. Ghosh S, Manvikar S, Ray-Chaudhuri N, Birch M. Efficacy of transscleral diode laser cyclophotocoagulation in patients with good visual acuity. Eur J Ophthalmol. 2014;24:375–81. 19. Pastor SA, Singh K, Lee DA, Juzych MS, Lin SC, Netland PA, et al. Cyclophotocoagulation: a report by the American Academy of Ophthalmology. Ophthalmology. 2001;108:2130–8. 20. McKelvie PA, Walland MJ. Pathology of cyclodiode laser: a series of 9 enucleated eyes. Br J Ophthalmol. 2002;86:381–6. 21. Noecker RJ, Kelly T, Patterson E, Herrygers LA. Diode laser contact transscleral cyclophotocoagulation: getting the most from the G-probe. Ophthalmic Surg Lasers Imaging. 2004;35:124–30. 22. Chang SH, Chen YC, Li CY, Wu SC. Contact diode laser transscleral cyclophotocoagulation for refractory glaucoma: comparison of 2 treatment protocols. Can J Ophthalmol. 2004;39:511–6. 23. Murphy CC, Burnett CA, Spry PG, Broadway DC, Diamond JP. A 2 centre study of the dose–response relation for transscleral diode laser cyclophotocoagulation in refractory glaucoma. Br J Ophthalmol. 2003;87:1252–7. 24. Hauber FA, Scherer WJ. Influence of total energy delivery on success rate after contact diode laser transscleral cyclophotocoagulation: a retrospective case review and meta-analysis. J Glaucoma. 2002;11:329–33. ˜ 25. Rebolleda G, Munoz FJ, Murube J. Audible pops during cyclodiode procedures. J Glaucoma. 1999;8:177–83. 26. Schuman JS, Noecker RJ, Puliafito CA, Jacobson JJ, Shepps GJ, Wang N. Energy levels and probe placement in contact transscleral semiconductor diode laser cyclophotocoagulation in human cadaver eyes. Arch Ophthalmol. 1991;109:1534–8. 27. Ishida K. Update on results and complications of cyclophotocoagulation. Curr Opin Ophthalmol. 2013;24:102–10. 28. Johnson SM. Neurotrophic corneal defects after diode laser cycloablation. Am J Ophtalmol. 1998;126:725–7. 29. Yildirim N, Yalvac IS, Sahin A, Ozer A, Bozca T. A comparative study between diode laser cyclophotocoagulation and the
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Ahmed glaucoma valve implant in neovascular glaucoma: a long-term follow-up. J Glaucoma. 2009;18:192–6. 30. Weissman SS, Asbell PA. Effects of topical timolol (0.5%) and betaxolol (0.5%) on corneal sensitivity. Br J Ophthalmol. 1990;74:409–12.
31. Palmer DJ, Cohen J, Torczynski E, Deutsch TA. Transscleral diode laser cyclophotocoagulation on autopsy eyes with abnormally thinned sclera. Ophthalmic Surg Lasers. 1997;28:495–500.
7
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Original article
Neurotrophic keratitis after transscleral diode laser cyclophotocoagulation夽,夽夽 Á. Fernández-Vega González a,b,∗ , R.I. Barraquer Compte a,b , A.L. Cárcamo Martínez b , M. Torrico Delgadillo b , M.F. de la Paz a,b a b
Centro de Oftalmología Barraquer, Barcelona, Spain Institut Universitari Barraquer, Universidad Autónoma de Barcelona, Barcelona, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history:
Objective: To study the relationship between treatment with diode laser transscleral
Received 25 May 2015
cyclophotocoagulation and development a neurotrophic keratitis due to the damage of the
Accepted 1 December 2015
sensitive corneal innervation.
Available online xxx
Methods: A study was conducted on 5 eyes of 5 patients who were treated with diode laser transscleral cyclophotocoagulation and soon developed neurotrophic ulcers. Personal char-
Keywords:
acteristics of the patients were collected, as well as refraction and risk factors for corneal
Neurotrophic keratitis
hypoesthesia, and the parameters of the laser used in the surgery.
Transscleral cyclophotocoagulation
Results: It was found that the 5 patients had predisposing factors of corneal hypoesthesia
Neurotrophic corneal ulcer
prior to surgery (chronic use of topical beta blockers, surgery with corneal incisions, diabetes mellitus, or corneal dystrophies); however none had developed neurotrophic keratitis until the cyclophotocoagulation was performed. It also showed that 4 of them were highly myopic, and they all were treated with high laser parameters (with an average of 2880 mW for 3 s at an average surface of 275◦ ), triggering neurotrophic ulcers between 10 and 35 days after surgery. Conclusion: Neurotrophic keratitis is a rare complication that can occur after diode laser transscleral cyclophotocoagulation, secondary to the damage of the long ciliary nerves. The emergence of this disorder can be triggered by the existence of previous risk factors, including high myopia, thus it is important to respect the recommended treatment parameters to prevent the development of this disorder. ˜ © 2015 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
夽 Please cite this article as: Fernández-Vega González Á, Barraquer Compte RI, Cárcamo Martínez AL, Torrico Delgadillo M, de la Paz MF. Queratitis neurotrófica posciclofotocoagulación transescleral con láser diodo. Arch Soc Esp Oftalmol. 2016. http://dx.doi.org/10.1016/j.oftal.2015.12.001 夽夽 Partially presented in the Master’s Degree in Corneal and Ocular Surface Pathology at the Autonomous University of Barcelona and Barraquer University Institute and the Congress of the Catalan Society of Ophthalmology, Barcelona, November 2015. ∗ Corresponding author. E-mail address: [email protected] (Á. Fernández-Vega González). ˜ 2173-5794/© 2015 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
OFTALE-924; No. of Pages 7
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Queratitis neurotrófica posciclofotocoagulación transescleral con láser diodo r e s u m e n Palabras clave:
Objetivo: Estudiar la relación existente entre el tratamiento con ciclofotocoagulación trans-
Queratitis neurotrófica
escleral con láser de diodo y el desarrollo de queratitis neurotróficas por lesión de la
Ciclofotocoagulación
inervación sensitiva corneal.
transescleral
Métodos: Se han estudiado 5 ojos de 5 pacientes que fueron tratados con ciclofotocoagulación
Úlcera corneal neurotrófica
transescleral con láser de diodo y al poco tiempo desarrollaron úlceras neurotróficas. Se han recogido las diferentes características personales de los pacientes, incluyendo refracción y factores de riesgo de hipoestesia corneal, así como los parámetros de láser empleados en el tratamiento. Resultados:
Se comprobó que los 5 pacientes presentaban factores predisponentes de
hipoestesia corneal previos a la cirugía (uso de betabloqueantes tópicos crónicos, cirugías corneales, diabetes mellitus o distrofias corneales). Sin embargo, ninguno había desarrollado queratitis neurotróficas hasta el momento de la ciclofotocoagulación. Se evidenció, además, que 4 de ellos eran altos miopes y que todos ellos fueron tratados con parámetros elevados de láser (2.880 mW por 3 s, en una superficie de 275◦ de media), y se desencadenaron úlceras neurotróficas entre los 10 y los 35 días después de la cirugía. Conclusiones: La queratopatía neurotrófica es una complicación poco frecuente que puede aparecer tras la ciclofotocoagulación transescleral con láser de diodo, debido a la lesión secundaria de los nervios ciliares largos. La aparición de esta se puede ver favorecida por la existencia de factores de riesgo previos, entre los que hay que incluir la alta miopía. Es crucial respetar los parámetros de tratamiento recomendados, para evitar la aparición de esta dolencia. ˜ de Oftalmología. Publicado por Elsevier España, S.L.U. Todos © 2015 Sociedad Espanola los derechos reservados.
Introduction The cornea is one of the most densely innervated tissues in the human body. Innervation is mainly by the ophthalmic division of the trigeminal nerve which, through the long ciliary nerves, exerts a trophic influence on the corneal epithelium.1–5 Alteration of this sensory innervation can lead to loss of that trophic influence, causing a deficiency in the blink and tear reflexes, a reduction in cell metabolism and decreased proliferation of basal cells, which can result in epithelial defects and affect the healing of the cornea. All this can lead to neurotrophic keratitis, with the development of recurrent and difficult-to-treat corneal ulcers.6–9 The most common cause is herpes simplex or herpes zoster virus eye infection, but any illness, surgical or traumatic procedure that damages corneal sensory innervation can lead to neurotrophic keratitis.6,10–14 Diode-laser transscleral cyclophotocoagulation is a method used to reduce intraocular pressure (IOP) in patients with glaucoma which destroys the secretory ciliary epithelial cells, thereby reducing the secretion of aqueous humour. The radiation produced by the diode laser interacts with the target biological tissues and causes a photothermal effect which generates photocoagulation, necrosis and inflammation of the tissues.15–20 Although treatment in each case has to be individualised, when performing transscleral cyclophotocoagulation using a continuous wavelength semiconductor laser diode that emits a wavelength of 810 nm, it is recommended that the contact probe be placed 1–1.5 mm posterior to the
limbus with no more than 24 hits in an area of 170◦ –270◦ . Moreover, it is advisable to use powers of 1500–2500 mW for 1.5–2.5 s (2.25–6.25 J), avoiding the 3- and 9-o’clock meridians as far as possible in order not to damage the vessels and long ciliary nerves. A standard technique would be to start using low powers of around 1500 mW for 1.5 s (2.25 J), and then gradually increase until an audible “pop” sound is heard, indicating thermal decomposition of the tissues, then lower the power. However, it is recommended not to exceed 2500 mW for 2.5 s (6.25 J) as the chances of complications increase.15–17,21–26 The complications of this treatment published so far include anterior uveitis, eye pain, temporary increase in IOP, choroidal detachment, chronic hypotonia, decompensated corneal graft, macular pucker, cystoid macular oedema, hyphema, vitreous haemorrhage, loss of visual acuity, retinal detachment, conjunctival and scleral burns, corneal oedema, sympathetic ophthalmia and phthisis bulbi.15–17,27 There is very little literature on the relationship between transscleral diode laser cyclophotocoagulation and neurotrophic keratitis,28,29 so the possible role of this technique in the development of neurotrophic ulcers is not fully understood.
Subjects, materials and methods This article presents the retrospective descriptive case series study in which we reviewed patients with glaucoma at the
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Fig. 1 – Patient 1. 2.5 mm × 1.5 mm neurotrophic corneal ulcer stained with fluorescein 17 days after cyclophotocoagulation.
Barraquer Ophthalmology Centre who were treated with transscleral cyclophotocoagulation and shortly thereafter developed neurotrophic keratitis. We found 5 eyes in 5 patients who developed neurotrophic ulcers soon after cyclodestructive treatment and studied their different personal characteristics, including gender, age, type of glaucoma, refraction, previous medical and surgical history and previous medical treatments, as well as risk factors for corneal hypoaesthesia. The laser parameters used to perform the cyclophotocoagulation were recorded, with the number of hits made, the extent of the area treated in degrees and the power used. The surgical technique performed on all the patients included in the study was transscleral cyclophotocoagulation with continuous-wave semiconductor laser diode emitting at 810 nm. The laser system used was an Iris Medical Oculight SL® by IRIDEX with a G-Probe TM. We determined the time from surgery until onset of neurotrophic defects and the treatment received and outcome. Two of the patients included in the study had died and the other 3 continued under follow-up at our centre.
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Fig. 2 – Patient 1. Resolution of neurotrophic corneal ulcer one and a half months later, with positive fluorescein closure line.
Fig. 3 – Patient 2. 6 mm × 3 mm neurotrophic corneal ulcer stained with fluorescein 18 days after cyclophotocoagulation.
Results The study included 5 patients, 3 male and 2 female, with a mean age of 63.2 years. All 5 had chronic open-angle glaucoma and had been under follow-up for an average of 12.2 years prior to the cyclophotocoagulation treatment. During that time, they were all treated long-term with beta-blockers, prostaglandins and at least one other topical hypotensive agent (an alpha-agonist or a carbonic anhydrase inhibitor). In 2 cases, filtering surgery was required to control their IOP (one required 2 trabeculectomies 6 and 3 years before the cyclophotocoagulation (Figs. 1 and 2) and the other had an Ahmed valve implanted 3 years beforehand). Only 1 of the patients (Figs. 3 and 4) had not previously had surgery on the eye on which the cyclodestructive procedure was applied. In the other cases, in addition to the filtering surgery already mentioned, 3 patients had undergone
Fig. 4 – Patient 2. Corneal erosion of 0.5 mm, one and a half months after onset.
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Fig. 5 – Patient 3. Residual corneal leucoma after neurotrophic corneal ulcer.
extracapsular cataract extraction (10, 27 and 36 years before the cyclodestructive treatment), and one had also required penetrating keratoplasty twice (first for bullous keratopathy and then for fungal keratitis), the second of which was a year before the cyclophotocoagulation (Fig. 5). One of the cases also had corneal dystrophy, diagnosed 30 years previously, but which had not caused any symptoms in all that time. Another important finding was that 3 of the patients had high myopia with a mean spherical equivalent of −7.3 diopters (D). The refraction was not available for the other 2 patients, but for one of them, who had Down’s syndrome, we did have the biometry measurement (Figs. 6 and 7), 24.98 mm, which indicated axial myopia. In terms of general previous medical history, one of the patients had been diagnosed with type 2 diabetes 3 years previously, although there had been no eye involvement up to the time of treatment (Figs. 8 and 9). Focusing on the laser parameters used during cyclophotocoagulation, we found that the mean number of hits was 22.4 on an average surface area of 274◦ (with a range of 200–360◦ ). The mean energy used in these cases was 2880 mW for 3 s
Fig. 6 – Patient 4. Vascularised residual leucoma after multiple neurotrophic keratitis.
Fig. 7 – Patient 4. Phthisis bulbi.
(8.6 J) with a range of 7.5–9 J; 3 patients received hits over 270◦ or more, with 3000 mW for 3 s (9 J) (Table 1). After the cyclophotocoagulation all the patients developed neurotrophic keratitis, with the first epithelial defects appearing, on average, 22 days (range 10–35 days) posttreatment. In all cases, the ulcers were treated with topical artificial tears, topical antibiotics and therapeutic contact lens or eyepatch. Four of the patients also required blood components (50% autologous serum or platelet-rich plasma) and one was also treated with minoarte (carboxymethyl glucose sulfate). The neurotrophic defects took an average of 36 days to clear up. All the patients had further episodes of recurrent corneal ulcers which, in 3 cases, resulted in residual leucoma affecting visual acuity. The Down’s syndrome patient’s eye was the one with the worst prognosis, although not because of neurotrophic keratitis, but because he suffered total retinal detachment that led to phthisis bulbi. Two of the patients required a second cyclophotocoagulation session due to poor control of their IOP and, once again, high parameters were used (average of 17.5 hits over an area
Fig. 8 – Patient 5. 6 mm × 4.5 mm neurotrophic corneal ulcer stained with fluorescein, one month after cyclophotocoagulation.
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Table 1 – Characteristics of the study patients and laser parameters used. Patient
Gender
Age
Corneal hypoaesthesia RF
1 2 3 4 5 Mean
Female Male Male Male Female
74 64 78 29 71 63.2
BB, Trabeculectomy BB BB, ECCE, PK BB, ECCE BB, ECCE, corneal dystrophy, DM2
No. of hits 26 20 11 30 25 22.4
Degrees
Potency (mW)
270 270 200 270 360 274
2900 3000 3000 3000 2500 2880
Duration (s) 3 3 3 3 3 3
T◦ onset (days) 17 18 10 35 30 22
BB, beta-blockers; DM2, type 2 diabetes mellitus; ECCE, extracapsular cataract extraction; RF, risk factors; PK, penetrating keratoplasty; T◦ onset, time neurotrophic ulcers appeared.
Fig. 9 – Patient 5. Residual leucoma after resolution of the condition one month after onset.
of 195◦ and mean power of 2925 mW for 3 s). Again, in the following month, both patients developed neurotrophic corneal defects which continued to recur over the next few years.
Discussion The aim of this study was to analyse the relationship between treatment with diode laser transscleral cyclophotocoagulation and development of neurotrophic keratitis. It is well known that long-term use of topical beta-blockers, corneal surgery with large incisions, diabetes mellitus and some corneal dystrophies are predisposing and trigger factors for corneal hypoaesthesia.16,30 In our series, we found that 2 patients had one of these risk factors (long-term topical instillation of beta-blockers), 2 patients had 2 (long-term topical instillation of beta-blockers and eye surgery with large corneal incisions – ECCE and penetrating keratoplasty) and the fifth patient had 4 (long-term topical beta-blockers, ECCE, diabetes mellitus and corneal dystrophy). However, they had all had been living with these risk factors for years without developing neurotrophic keratitis, until they had cyclophotocoagulation. Even the patient who had undergone 2 keratoplasties and an ECCE, who was the one with the shortest free interval between the risk factor and the cyclophotocoagulation, went a year after the last transplant without any neurotrophic damage. We would
therefore argue that these factors may have been predisposing factors, but they were not what triggered the neurotrophic keratitis. The trigger in our patients was the transscleral cyclophotocoagulation which, due to the application of high laser power (8.6 J on average) over a large area (270–360◦ ), when added to the predisposing factors, caused damage to the long ciliary nerves and resulted in neurotrophic keratopathy. As has been demonstrated, if radiation is applied for longer than recommended, heat conduction can cause raising of the temperature beyond the irradiated target tissue, indirectly causing undesired effects in adjacent non-target regions. Add to that the application of a high average power level, and we create a very harmful vaporisation effect, in which the tissue temperature increases and mechanical rupture and thermal decomposition of tissues occur, the sign of which is the audible “pop” we mentioned earlier.20,22,23,25,26 This situation requires lower laser power as described in the application technique. In the study by Schuman et al.26 in 1991, the effect of transscleral cyclophotocoagulation was analysed on human cadaver eyes using different energy levels. The authors concluded that, above 5 J, explosive tissue damage occurs and that the optimum power setting for diode laser cyclophotocoagulation is between 3 and 4.5 J. As discussed earlier, most experts recommend not exceeding 2500 mW for 2.5 s (6.25 J) and not treating an area greater than 270◦ , as doing otherwise can increase the risk of complications.15–17,21–24,26 However, in our study, the mean energy used (2880 mW for 3 s [8.6 J over 274◦ ]) was considerably higher than the figure recommended. In an experimental model with 6 mice subjected to stereotactic trigeminal electrolysis,14 the corneal nerves were not histologically recognisable at 48 h. In that study, over the following 7 days, a reduction in basal epithelial cell proliferation was observed with increase in cell apoptosis in all the layers of the cornea. In our patients, the diode laser damaged the sensory nerve fibres, with the result that the undamaged innervation remaining in the areas not irradiated with the laser was not enough to maintain the epithelium, and they all developed neurotrophic keratitis over the following 10–35 days. Histology studies would be required to determine the extent of the damage to corneal innervation and be able to demonstrate the damage to the long ciliary nerves after the cyclophotocoagulation, but we believe the most plausible explanation to be that the damage was caused by a hyperthermia lesion due to the excessive energy levels used in the treatment.
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Another finding we consider relevant is that 4 of the patients had high myopia (spherical equivalent −7.3 D). This is important, since people with high myopia have thinner sclera than normal, which means that the long ciliary nerves, which in the ciliary body run through the suprachoroids and, as they approach the limbus, become integrated into the sclera,1–5 are more likely to be damaged by transscleral cyclophotocoagulation. In 1997, Palmer et al. showed in their experiment31 that differences in scleral thickness must be taken into account in the energy to be used with cyclophotocoagulation, since patients with thinner sclera are more likely to suffer greater tissue damage. Accordingly, high myopia must also be taken into account, as it may act as an additional risk factor. We were able to conclude that neurotrophic keratopathy is a rare complication that can occur after laser diode transscleral cyclophotocoagulation as a result of damage to the long ciliary nerves. It may be more likely in patients who already have risk factors prior to the treatment, such as the use of topical beta-blockers, previous eye surgery, diabetes mellitus, corneal dystrophies and high myopia. To avoid complications with this technique, it is crucial to respect the recommended treatment parameters. Particular care should above all be taken with patients who have the above risk factors, and we recommend using lower parameters in terms of area and power. If neurotrophic keratitis develops, blood components and carboxymethyl glucose sulfate can be helpful for resolving the disorder.
Conflict of interest The authors have no commercial interests and have received no financial support.
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