CONSULTATION SECTION
The right eye with 20/16 acuity should not be treated for the residual haze, which will decrease in time. Joseph Frucht-Pery, MD Denise Wajnsztajn, MD Jerusalem, Israel
REFERENCES 1. Reviglio VE, Rana TS, Li QJ, Ashraf MF, Daly MK, O’Brien TP. Effects of topical nonsteroidal antiinflammatory drugs on the expression of matrix metalloproteinases in the cornea. J Cataract Refract Surg 2003; 29:989–997 2. Reviglio VE, Hakim MA, Song JK, O’Brien TP. Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea. BMC Ophthalmol 2003; 3:10. Available at: http:// www.biomedcentral.com/content/pdf/1471-2415-3-10.pdf. Accessed December 20, 2013 3. Seitz B, Sorken K, LaBree LD, Garbus JJ, McDonnell PJ. Corneal sensitivity and burning sensation; comparing topical ketorolac and diclofenac. Arch Ophthalmol 1996; 114:921–924
- From the OCT image, it appears as though the opacity is a hypertrophic scar rather than haze within the stroma. The overlying epithelium is slightly thinned, and the resulting topography is quite regular. The UDVA is 20/16. Six months postoperatively, wound healing is not complete. Over the next 6 months. I would presume the scar would fade somewhat and thin slightly, resulting in less photophobia and hazy vision. I would recommend that the patient wait for natural improvement in visual acuity. If the patient does not accept this, I would suggest transepithelial ablation of the scar, probably performed as incremental transepithelial PTK. Preoperatively, the patient must be given clear and detailed information and told that spontaneous improvement might occur and that there is an increased risk for delayed wound healing, which could compromise the result. I would also consider applying MMC 0.02% for 20 seconds after ablation just at the denuded stroma. Normally, I use chloramphenicol and fluorometholone drops and nonpreserved diclofenac drops 4 times daily. In this case, I would consider using chloramphenicol ointment (instead of drops) 3 to 4 times daily and follow the patient daily until healing. Normally, I do not use bandage contact lenses postoperatively because sterile infiltrates and keratitis are more common with their use. Often, patients with a bandage lens develop some irritation 2 or 3 days postoperatively, and I prefer to take an additional look at those patients. However, my patients often live quite far from the clinic, and taking this additional look is
505
logistically difficult. Thus, I sometimes place bandage contact lenses postoperatively. If healing is delayed, I first change to chloramphenicol ointment and reduce the fluorometholone and diclofenac. If this does not improve healing, I apply a contact lens. If healing is still not complete within 4 days, I use serum drops (allogeneic; prepared at the university hospital clinical immunologic department) 8 times daily. If there is still no improvement over 2 weeks, I would apply an amniotic bandage membrane over the cornea. Before treating the left eye, I would measure tear production and quality (Schirmer test and tear breakup time) and measure corneal sensitivity (Cochet-Bonnet). If these functions are normal, I would suggest transepithelial PRK or small-incision lenticule extraction because the latter does not involve creation of an epithelial defect, such as in PRK, or a flap, such as in LASIK. In either case, I would follow the patient closely postoperatively to ensure proper healing. Although the wound-healing response of the 2 eyes of the same individual is interdependent, there is a good chance this patient will have a satisfying result in the left eye. Jesper Hjortdal, MD, PhD Aarhus, Denmark
- Preoperatively, the case appears to be a straightforward PRK treatment to correct myopia in the right eye of a young patient. The postoperative course, however, is complicated by severely delayed epithelial healing and mild central stromal haze formation. Six months postoperatively, the UDVA is excellent, the corneal topography is normal, and there appears to be no unforeseen loss of stromal tissue, as can occur in an inflammatory reaction. The corneal OCT is normal, and the slitlamp image shows superficial central scar formation that is clinically significant given the patient’s reports of hazy vision and photophobia. The good visual recovery over the first 6 months warrants a conservative approach. I would prescribe topical prednisolone 4 times a day (tapering over several weeks to months according to the clinical course) and monitor contrast sensitivity and intraocular pressure. If there is no clinical or subjective improvement, a secondary procedure with epithelial abrasion, PTK, and application of MMC 0.02% for 30 seconds would be a good option. Autologous serum drops can be used to promote epithelial healing.1 Before further corneal procedures (PTK in the right eye or myopia correction in the left eye) are performed,
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the patient should quit smoking.2 Also, oral administration of omega 3 fatty acids and the use of high-oxygen permeable silicone hydrogel contact lenses may help speed epithelial healing.3,4 Once the right eye has recovered to a satisfactory level, treatment in the fellow eye can be performed. I would advise transepithelial PRK, which is a 1-step treatment modality available on the laser machine that was used in the first eye. Transepithelial PRK makes the smallest epithelial abrasion on any optical zone and hence heals more quickly than alcoholassisted manual abrasion. Also, I would use MMC to prevent haze formation. Alternatively, LASIK is a good option. However, I do not advocate the use of different procedures in each eye of 1 patient. Photorefractive keratectomy in a young patient with low myopia is a safe and effective approach. Typically, young patients recover quickly. Delayed epithelial healing is a fairly rare condition that may occur after surface ablation. Michiel H.A. Luger, MD Naarden, The Netherlands
REFERENCES 1. Anitua E, Muruzabal F, Alcalde I, Merayo-Lloves J, Orive G. Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery. Exp Eye Res 2013; 115:153–161 2. Roszkowska AM, De Grazia L, Visalli M, Mondello M, Teti D, Venza M, Venza I. Contact lens wearing and chronic cigarette smoking positively correlate with TGF-b1 and VEGF tear levels and impaired corneal wound healing after photorefractive keratectomy. Curr Eye Res 2013; 38:335–341 3. Ong NH, Purcell TL, Roch-Levecq A-C, Wang D, Isidro MA, Bottos KM, Heichel CW, Schanzlin DJ. Epithelial healing and visual outcomes of patients using omega-3 oral nutritional supplements before and after photorefractive keratectomy: a pilot study. Cornea 2013; 32:761–765 4. Plaka A, Grentzelos MA, Astyrakakis NI, Kymionis GD, Pallikaris IG, Plainis S. Efficacy of two silicone-hydrogel contact lenses for bandage use after photorefractive keratectomy. Cont Lens Anterior Eye 2013; 36:243–246
- This case of early mild stromal haze is typical of delayed epithelial healing after PRK for mild myopic correction. It illustrates the need for refractive surgeons to understand corneal wound healing at the cellular and molecular biology level.1 The patient has a history of contact lens and smoking; both are related to significant changes in tear cytokine network epithelialization, impairing corneal epithelial healing and causing early haze formation after PRK.2 Roszkowska et al.2 found contact lens use to
be positively correlated with transforming growth factor (TGF)-b1 amounts and early haze formation and chronic smoking to be positively correlated with vascular endothelial growth factor production and delayed reepithelialization. It is important to determine whether the patient was exposed to cigarette smoke during the healing process. A study of mice3 found cigarette smoking was associated with defective formation of the fibronectin layer in the wounded area and with accumulation of neutrophils in the stroma beneath the deepithelialized area. Fibronectin is an extracellular matrix (ECM) molecule that is critical for epithelial cell migration and the formation of the epithelial basement membrane; thus, this impairment is related to delayed corneal epithelial healing. Also, anther study4 elucidated the role of the generation of corneal myofibroblasts in the development of haze after surgery or other types of injury and the importance of the basement membrane, which functions as a barrier between the epithelium and stroma and modulates the cytokines that promote and maintain myofibroblasts (eg, TGF- b1, platelet-derived growth factor, interleukin-1). Thus, although functional defects in basement membrane formation lead to prolonged elevation of cytokine levels in the stroma necessary to promote differentiation of myofibroblasts, repair of the epithelial basement membrane determines elimination of myofibroblasts so that repopulating keratocytes subsequently reorganize ECM to reestablish transparency.5 There is no mention of whether MMC was used. Although MMC has been associated with slightly longer epithelial healing,6 it has been associated with a lower risk for corneal haze.7,8 Postoperatively, a bandage contact lens was applied and the patient received topical fluorometholone and ketorolac tromethamine 0.4%. Ketorolac, like most topical NSAIDs, has been associated with corneal wound-healing problems and melting.9 Once delayed epithelial healing is noticed, the proper management is to discontinue NSAIDs and reduce the steroid dosage. Although topical corticosteroids may delay epithelial healing, they are important to suppress stromal scarring and fibrosis and should usually be continued. Along with preservative-free artificial tears with hyaluronate, which have a positive impact on corneal epithelial healing,10 I would consider autologous serum in such cases.11,12 Considering the presentation of the case, I would like to have total wavefront data and a proper assessment of the ocular surface. Considering the natural history of corneal haze, I would not consider surgical treatment. Therapeutic ablation would be an option at least 1 year after the first procedure.13 I would recommend omega-3 essential fatty acid supplementation along
J CATARACT REFRACT SURG - VOL 40, MARCH 2014
The right eye with 20/16 acuity should not be treated for the residual haze, which will decrease in time. Joseph Frucht-Pery, MD Denise Wajnsztajn, MD Jerusalem, Israel
REFERENCES 1. Reviglio VE, Rana TS, Li QJ, Ashraf MF, Daly MK, O’Brien TP. Effects of topical nonsteroidal antiinflammatory drugs on the expression of matrix metalloproteinases in the cornea. J Cataract Refract Surg 2003; 29:989–997 2. Reviglio VE, Hakim MA, Song JK, O’Brien TP. Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea. BMC Ophthalmol 2003; 3:10. Available at: http:// www.biomedcentral.com/content/pdf/1471-2415-3-10.pdf. Accessed December 20, 2013 3. Seitz B, Sorken K, LaBree LD, Garbus JJ, McDonnell PJ. Corneal sensitivity and burning sensation; comparing topical ketorolac and diclofenac. Arch Ophthalmol 1996; 114:921–924
- From the OCT image, it appears as though the opacity is a hypertrophic scar rather than haze within the stroma. The overlying epithelium is slightly thinned, and the resulting topography is quite regular. The UDVA is 20/16. Six months postoperatively, wound healing is not complete. Over the next 6 months. I would presume the scar would fade somewhat and thin slightly, resulting in less photophobia and hazy vision. I would recommend that the patient wait for natural improvement in visual acuity. If the patient does not accept this, I would suggest transepithelial ablation of the scar, probably performed as incremental transepithelial PTK. Preoperatively, the patient must be given clear and detailed information and told that spontaneous improvement might occur and that there is an increased risk for delayed wound healing, which could compromise the result. I would also consider applying MMC 0.02% for 20 seconds after ablation just at the denuded stroma. Normally, I use chloramphenicol and fluorometholone drops and nonpreserved diclofenac drops 4 times daily. In this case, I would consider using chloramphenicol ointment (instead of drops) 3 to 4 times daily and follow the patient daily until healing. Normally, I do not use bandage contact lenses postoperatively because sterile infiltrates and keratitis are more common with their use. Often, patients with a bandage lens develop some irritation 2 or 3 days postoperatively, and I prefer to take an additional look at those patients. However, my patients often live quite far from the clinic, and taking this additional look is
505
logistically difficult. Thus, I sometimes place bandage contact lenses postoperatively. If healing is delayed, I first change to chloramphenicol ointment and reduce the fluorometholone and diclofenac. If this does not improve healing, I apply a contact lens. If healing is still not complete within 4 days, I use serum drops (allogeneic; prepared at the university hospital clinical immunologic department) 8 times daily. If there is still no improvement over 2 weeks, I would apply an amniotic bandage membrane over the cornea. Before treating the left eye, I would measure tear production and quality (Schirmer test and tear breakup time) and measure corneal sensitivity (Cochet-Bonnet). If these functions are normal, I would suggest transepithelial PRK or small-incision lenticule extraction because the latter does not involve creation of an epithelial defect, such as in PRK, or a flap, such as in LASIK. In either case, I would follow the patient closely postoperatively to ensure proper healing. Although the wound-healing response of the 2 eyes of the same individual is interdependent, there is a good chance this patient will have a satisfying result in the left eye. Jesper Hjortdal, MD, PhD Aarhus, Denmark
- Preoperatively, the case appears to be a straightforward PRK treatment to correct myopia in the right eye of a young patient. The postoperative course, however, is complicated by severely delayed epithelial healing and mild central stromal haze formation. Six months postoperatively, the UDVA is excellent, the corneal topography is normal, and there appears to be no unforeseen loss of stromal tissue, as can occur in an inflammatory reaction. The corneal OCT is normal, and the slitlamp image shows superficial central scar formation that is clinically significant given the patient’s reports of hazy vision and photophobia. The good visual recovery over the first 6 months warrants a conservative approach. I would prescribe topical prednisolone 4 times a day (tapering over several weeks to months according to the clinical course) and monitor contrast sensitivity and intraocular pressure. If there is no clinical or subjective improvement, a secondary procedure with epithelial abrasion, PTK, and application of MMC 0.02% for 30 seconds would be a good option. Autologous serum drops can be used to promote epithelial healing.1 Before further corneal procedures (PTK in the right eye or myopia correction in the left eye) are performed,
J CATARACT REFRACT SURG - VOL 40, MARCH 2014
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CONSULTATION SECTION
the patient should quit smoking.2 Also, oral administration of omega 3 fatty acids and the use of high-oxygen permeable silicone hydrogel contact lenses may help speed epithelial healing.3,4 Once the right eye has recovered to a satisfactory level, treatment in the fellow eye can be performed. I would advise transepithelial PRK, which is a 1-step treatment modality available on the laser machine that was used in the first eye. Transepithelial PRK makes the smallest epithelial abrasion on any optical zone and hence heals more quickly than alcoholassisted manual abrasion. Also, I would use MMC to prevent haze formation. Alternatively, LASIK is a good option. However, I do not advocate the use of different procedures in each eye of 1 patient. Photorefractive keratectomy in a young patient with low myopia is a safe and effective approach. Typically, young patients recover quickly. Delayed epithelial healing is a fairly rare condition that may occur after surface ablation. Michiel H.A. Luger, MD Naarden, The Netherlands
REFERENCES 1. Anitua E, Muruzabal F, Alcalde I, Merayo-Lloves J, Orive G. Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery. Exp Eye Res 2013; 115:153–161 2. Roszkowska AM, De Grazia L, Visalli M, Mondello M, Teti D, Venza M, Venza I. Contact lens wearing and chronic cigarette smoking positively correlate with TGF-b1 and VEGF tear levels and impaired corneal wound healing after photorefractive keratectomy. Curr Eye Res 2013; 38:335–341 3. Ong NH, Purcell TL, Roch-Levecq A-C, Wang D, Isidro MA, Bottos KM, Heichel CW, Schanzlin DJ. Epithelial healing and visual outcomes of patients using omega-3 oral nutritional supplements before and after photorefractive keratectomy: a pilot study. Cornea 2013; 32:761–765 4. Plaka A, Grentzelos MA, Astyrakakis NI, Kymionis GD, Pallikaris IG, Plainis S. Efficacy of two silicone-hydrogel contact lenses for bandage use after photorefractive keratectomy. Cont Lens Anterior Eye 2013; 36:243–246
- This case of early mild stromal haze is typical of delayed epithelial healing after PRK for mild myopic correction. It illustrates the need for refractive surgeons to understand corneal wound healing at the cellular and molecular biology level.1 The patient has a history of contact lens and smoking; both are related to significant changes in tear cytokine network epithelialization, impairing corneal epithelial healing and causing early haze formation after PRK.2 Roszkowska et al.2 found contact lens use to
be positively correlated with transforming growth factor (TGF)-b1 amounts and early haze formation and chronic smoking to be positively correlated with vascular endothelial growth factor production and delayed reepithelialization. It is important to determine whether the patient was exposed to cigarette smoke during the healing process. A study of mice3 found cigarette smoking was associated with defective formation of the fibronectin layer in the wounded area and with accumulation of neutrophils in the stroma beneath the deepithelialized area. Fibronectin is an extracellular matrix (ECM) molecule that is critical for epithelial cell migration and the formation of the epithelial basement membrane; thus, this impairment is related to delayed corneal epithelial healing. Also, anther study4 elucidated the role of the generation of corneal myofibroblasts in the development of haze after surgery or other types of injury and the importance of the basement membrane, which functions as a barrier between the epithelium and stroma and modulates the cytokines that promote and maintain myofibroblasts (eg, TGF- b1, platelet-derived growth factor, interleukin-1). Thus, although functional defects in basement membrane formation lead to prolonged elevation of cytokine levels in the stroma necessary to promote differentiation of myofibroblasts, repair of the epithelial basement membrane determines elimination of myofibroblasts so that repopulating keratocytes subsequently reorganize ECM to reestablish transparency.5 There is no mention of whether MMC was used. Although MMC has been associated with slightly longer epithelial healing,6 it has been associated with a lower risk for corneal haze.7,8 Postoperatively, a bandage contact lens was applied and the patient received topical fluorometholone and ketorolac tromethamine 0.4%. Ketorolac, like most topical NSAIDs, has been associated with corneal wound-healing problems and melting.9 Once delayed epithelial healing is noticed, the proper management is to discontinue NSAIDs and reduce the steroid dosage. Although topical corticosteroids may delay epithelial healing, they are important to suppress stromal scarring and fibrosis and should usually be continued. Along with preservative-free artificial tears with hyaluronate, which have a positive impact on corneal epithelial healing,10 I would consider autologous serum in such cases.11,12 Considering the presentation of the case, I would like to have total wavefront data and a proper assessment of the ocular surface. Considering the natural history of corneal haze, I would not consider surgical treatment. Therapeutic ablation would be an option at least 1 year after the first procedure.13 I would recommend omega-3 essential fatty acid supplementation along
J CATARACT REFRACT SURG - VOL 40, MARCH 2014
