Reports Deep Anterior Lamellar Keratoplasty Using Fresh versus Cryopreserved Corneas Deep anterior lamellar keratoplasty (DALK) requires less stringent criteria for donor tissue quality, which is important in countries with a shortage of donor corneas. Long-term corneal preservation was initially introduced to protect the living endothelial cells from freezing damage. However, the subsequent studies demonstrate that long-term preservation by lyophilization or chemical glycerin dehydration effectively depletes donor cells leaving just a stromal collagen matrix for keratoplasty.1,2 Because DALK allows acellular tissues to be transplanted, a simpler method of long-term preservation in which no cryoprotectant is used can be adopted. To the best of our knowledge, no comparative studies have been performed to determine whether cryopreservation of donor grafts without the use of cryoprotectants gives rise to DALKappropriate tissue. We have evaluated the clinical outcomes and complications after DALK using cryopreserved corneal grafts and compare the results with those after penetrating keratoplasty (PK) and DALK using fresh grafts. In this retrospective, comparative study, keratoconic patients with poor spectacle-corrected visual acuity, rigid gas-permeable contact lens intolerance, or inappropriate contact lens fit were included. Inclusion also required a minimum follow-up of 12 months. Exclusion criteria included the coexistence of other ocular pathologies such as cataract, retinal disorders, glaucoma, and active vernal keratoconjunctivitis. An inability to achieve a bared Descemet’s membrane during DALK also resulted in patient exclusion. Overall, 61 consecutive eyes of 61 keratoconic patients underwent corneal transplantation: 18 (29.5%) eyes underwent PK (group 1), 28 (45.9%) eyes received Anwar’s DALK using a fresh corneal graft (group 2), and 15 (24.6%) eyes had Anwar’s DALK using a cryopreserved graft (group 3). We performed PK in advanced cases (n ¼ 17) when corneal stroma was very thin or there were deep stromal scars with Descemet’s membrane involvement, suggestive of previous hydrops. Additionally, in 1 case, DALK was converted to PK intraoperatively because of a large tear in the Descemet’s membrane. Fresh donor corneas were preserved at 4 C (Optisol-GS preservative; Chiron Vision, Irvine, CA) and cryopreserved donor corneas were stored from 44 to 148 days (mean, 81.628.3) as a whole globe at 70 C without the use of any cryoprotectant. On the day of surgery, the frozen whole globe was defrosted by first transferring to a refrigerator and then by reaching room temperature, each for a period of 1 hour, to decrease the thermal shock induced by rapid change of temperature. Mean patient age was 26.39.5 years in group 1, 27.37.4 years in group 2, and 26.58.7 years in group 3 (P ¼ 0.56). Mean follow-up period was 20.24.7, 19.43.5, and 20.35.0 months, respectively (P ¼ 0.65). Table 1 (available at http://aaojournal.org) summarizes demographic data and operative details. Final mean corrected distance visual acuity was 0.140.08 logarithm of minimum angle of resolution in group 1, 0.170.11 in
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group 2, and 0.200.09 in group 3 (P ¼ 0.22). Postoperative corrected distance visual acuity 20/40 was achieved in 100% of eyes in group 1, 89.3% of eyes in group 2, and 92.9% of eyes in group 3 (P ¼ 0.37). During the follow-up period, corrected distance visual acuities were comparable between the study groups at all examinations (Fig 1; available at http://aaojournal.org). Final spherical equivalent refraction was 1.492.05 diopter (D), 3.564.38 D, and e2.533.02 D, respectively (P ¼ 0.16). The mean keratometric astigmatism was 2.941.52 D in group 1, 3.411.95 D in group 2, and 2.431.10 D in group 3 (P ¼ 0.28). We did not observe any difference in postoperative complications between the study groups (Table 2; available at http:// aaojournal.org). Persistent epithelial defect (lasting >14 days) was less common with PK than with DALK using either fresh or cryopreserved grafts. However, the difference did not attain significance. Similarly, a nonsignificant increase in the frequency of suture complications was observed in group 3. Three eyes (16.7%) in group 1, 4 (14.3%) in group 2, and 1 (6.7%) in group 3 experienced an episode of nonendothelial (subepithelial) graft rejection (P ¼ 0.03). All rejection episodes were successfully treated with frequent topical betamethasone 0.1% eye drops. No graft failure was noticed at the final follow-up examination. The results of the current study demonstrate no differences in visual acuity, spherical equivalent refraction, or keratometric astigmatism between the study groups at the final follow-up examination, indicating that cryopreserved donors can provide similar clinical results to fresh corneal tissues used for PK and DALK. This observation is in agreement with the results of previous studies, which reported the results of DALK performed with acellular corneas using lyophilization3 or glycerin cryopreservation.1,4 Complications such as persistent epithelial defects and filamentary keratitis are more likely to develop when low-quality grafts are used in corneal transplantations. Similarly, we observed a higher rate of persistent epithelial defects and suture complications in the cryopreserved group, although the difference did not attain significance. In 46.7% of cases in group 3, persistent epithelial defects developed that could be simply managed by fitting extended-wear soft contact lenses or temporary tarsorrhaphy. This rate was reported as 4.6%5 and 15.4%1 in similar studies. Long-term preservation of the cornea by lyophilization and chemical glycerin dehydration eliminates donor cells and may significantly reduce or even eliminate the incidence of graft rejection after lamellar keratoplasty.1,2,4 Chen et al1 and Li et al4 observed no episode of graft rejection over a 2-year follow period after DALK using glycerol-cryopreserved corneal tissues with a mean storage time of 7.8 and 9.6 months, respectively. However, 1 eye transplanted with a cryopreserved cornea in our study experienced an episode of subepithelial rejection, suggesting the method used in this experience cannot completely eliminate rejection episodes. This observation can be attributed to the shorter storage time (2.7 months) in our experience. Additionally, different methods of corneal preservation can differently affect donor corneal antigenicity.2 In conclusion, cryopreserved corneal tissues can be used for DALK to treat keratoconus. The method of cryopreservation used is
Reports a simple way for long-term preservation of cornea, and does not require any lathing, lyophilization, or chemical agents, thereby reducing the tasks required for lenticules processing in the eye bank. The results of the current study, however, should be interpreted in the context of its limitations, including a nonrandomized retrospective design, limited sample size, and lack of data on postoperative endothelial cell counts.
MOHAMMAD ALI JAVADI, MD1 SEPEHR FEIZI, MD, MSC1 FATEMEH JAVADI, MD2 MOZHGAN REZAEI KANAVI, MD1 HASSAN GHASEMI, MD2 SETAREH KARIMDIZANI, MD1 FIROOZ MIRBABAEE, MD1 1 Ophthalmic Research Center and Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Ophthalmology, Shahed University of Medical Sciences, Tehran, Iran
Financial Disclosures: The study was financially supported by the Ophthalmic Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran.
References 1. Chen W, Lin Y, Zhang X, et al. Comparison of fresh corneal tissue versus glycerin-cryopreserved corneal tissue in deep anterior lamellar keratoplasty. Invest Ophthalmol Vis Sci 2010;51:775–81. 2. Li J, Shi S, Zhang X, et al. Comparison of different methods of glycerol preservation for deep anterior lamellar keratoplasty eligible corneas. Invest Ophthalmol Vis Sci 2012;53:5675–85. 3. Farias R, Barbosa L, Lima A, et al. Deep anterior lamellar transplant using lyophilized and Optisol corneas in patients with keratoconus. Cornea 2008;27:1030–6. 4. Li J, Yu L, Deng Z, et al. Deep anterior lamellar keratoplasty using acellular corneal tissue for prevention of allograft rejection in high-risk corneas. Am J Ophthalmol 2011;152:762–70. 5. Coombes AG, Kirwan JF, Rostron CK. Deep lamellar keratoplasty with lyophilised tissue in the management of keratoconus. Br J Ophthalmol 2001;85:788–91.
Appearance of Regressing Drusen on Adaptive Optics in Age-Related Macular Degeneration In age-related macular degeneration, material between the basal lamina of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch’s membrane are generally referred to as drusen.1 Although drusen “maturation” is characterized by accumulation of several layers of coiled membranous debris between the RPE and Bruch’s membrane,2 in drusen regression there is evidence not only of reduced formation of membranous debris, but also of its removal by macrophage. Material not removed develops calcification.2 Using tracked spectral-domain optical coherence tomographyd matched with regressing calcific drusen visualized as yellow-gray deposits with refractile areas on en face confocal scanning laser ophthalmoscope infrared (IR) or MultiColor imagesdwe recently described a laminar/multilaminar sub-RPE intense hyperreflectivity,
which we interpreted as layers of lipid mineralization, internal and external to the basement membrane, with different degrees of fragmentation.3 Adaptive optics (AO) fundus imaging allows an order of magnitude improvement of the lateral resolution of retinal images as compared with conventional en face imaging.4 We investigated en face AO imaging features of regressing drusen in 16 eyes of 12 consecutive patients (9 women; mean age 80.69.3 years). Flood illumination AO IR fundus images were obtained using an AO retinal camera (rtx1; Imagine Eyes, Orsay, France) that was previously decribed.5 In 9 of 16 eyes, en face AO IR imaging showed fused round or pisciform highly refractile lesions in correspondence of the spectral-domain optical coherence tomography featured laminar/ multilaminar sub-RPE intense hyperreflectivity (Fig 1; available at http://aaojournal.org). This could be interpreted as the in vivo visualization of mounds of membranous debris developing calcification, which, close to areas of atrophy, seem to be fused.2 Interestingly, in 7 of 16 eyes showing gray deposits with less refractile areas on en face confocal scanning laser ophthalmoscope IR imaging, the corresponding en face AO IR imaging revealed highly refractile interspersed tiny dots rather than fused round or pisciform, highly refractile lesions. In these eyes, the corresponding spectral-domain optical coherence tomography scans showed absence of laminar/multilaminar sub-RPE intense hyperreflectivity (Fig 2; available at http://aaojournal.org). This could be interpreted as the in vivo visualization of a further fragmentation and dispersion of the calcific material in advanced stages of regressing drusen. In conclusion, en face AO IR imaging allows us to distinguish fused, round or pisciform, highly refractile lesions, and highly refractile interspersed tiny dots as the characteristics of regressing drusen, possibly representing different stages in drusen calcification and regression.
GIUSEPPE QUERQUES, MD, PHD CYNTHIA KAMAMI-LEVY, MD ANOUK GEORGES, MD ALEXANDRE PEDINIELLI, MD ERIC H. SOUIED, MD, PHD Department of Ophthalmology, Centre Hospitalier Intercommunal de Creteil University Paris Est Creteil, Creteil, France
References 1. Spaide RF, Armstrong D, Browne R. Continuing medical education review: choroidal neovascularization in age-related macular degenerationewhat is the cause? Retina 2003;23: 595–614. 2. Sarks JP, Sarks SH, Killingsworth MC. Evolution of geographic atrophy of the retinal pigment epithelium. Eye 1988;2:552–77. 3. Querques G, Georges A, Ben Moussa N, et al. Appearance of regressing drusen on optical coherence tomography in age-related macular degeneration. Ophthalmology 2014;121: 173–9. 4. Liang J, Williams DR, Miller DT. Supernormal vision and highresolution retinal imaging through adaptive optics. J Opt Soc Am 1997;14:2884–92.
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group 2, and 0.200.09 in group 3 (P ¼ 0.22). Postoperative corrected distance visual acuity 20/40 was achieved in 100% of eyes in group 1, 89.3% of eyes in group 2, and 92.9% of eyes in group 3 (P ¼ 0.37). During the follow-up period, corrected distance visual acuities were comparable between the study groups at all examinations (Fig 1; available at http://aaojournal.org). Final spherical equivalent refraction was 1.492.05 diopter (D), 3.564.38 D, and e2.533.02 D, respectively (P ¼ 0.16). The mean keratometric astigmatism was 2.941.52 D in group 1, 3.411.95 D in group 2, and 2.431.10 D in group 3 (P ¼ 0.28). We did not observe any difference in postoperative complications between the study groups (Table 2; available at http:// aaojournal.org). Persistent epithelial defect (lasting >14 days) was less common with PK than with DALK using either fresh or cryopreserved grafts. However, the difference did not attain significance. Similarly, a nonsignificant increase in the frequency of suture complications was observed in group 3. Three eyes (16.7%) in group 1, 4 (14.3%) in group 2, and 1 (6.7%) in group 3 experienced an episode of nonendothelial (subepithelial) graft rejection (P ¼ 0.03). All rejection episodes were successfully treated with frequent topical betamethasone 0.1% eye drops. No graft failure was noticed at the final follow-up examination. The results of the current study demonstrate no differences in visual acuity, spherical equivalent refraction, or keratometric astigmatism between the study groups at the final follow-up examination, indicating that cryopreserved donors can provide similar clinical results to fresh corneal tissues used for PK and DALK. This observation is in agreement with the results of previous studies, which reported the results of DALK performed with acellular corneas using lyophilization3 or glycerin cryopreservation.1,4 Complications such as persistent epithelial defects and filamentary keratitis are more likely to develop when low-quality grafts are used in corneal transplantations. Similarly, we observed a higher rate of persistent epithelial defects and suture complications in the cryopreserved group, although the difference did not attain significance. In 46.7% of cases in group 3, persistent epithelial defects developed that could be simply managed by fitting extended-wear soft contact lenses or temporary tarsorrhaphy. This rate was reported as 4.6%5 and 15.4%1 in similar studies. Long-term preservation of the cornea by lyophilization and chemical glycerin dehydration eliminates donor cells and may significantly reduce or even eliminate the incidence of graft rejection after lamellar keratoplasty.1,2,4 Chen et al1 and Li et al4 observed no episode of graft rejection over a 2-year follow period after DALK using glycerol-cryopreserved corneal tissues with a mean storage time of 7.8 and 9.6 months, respectively. However, 1 eye transplanted with a cryopreserved cornea in our study experienced an episode of subepithelial rejection, suggesting the method used in this experience cannot completely eliminate rejection episodes. This observation can be attributed to the shorter storage time (2.7 months) in our experience. Additionally, different methods of corneal preservation can differently affect donor corneal antigenicity.2 In conclusion, cryopreserved corneal tissues can be used for DALK to treat keratoconus. The method of cryopreservation used is
Reports a simple way for long-term preservation of cornea, and does not require any lathing, lyophilization, or chemical agents, thereby reducing the tasks required for lenticules processing in the eye bank. The results of the current study, however, should be interpreted in the context of its limitations, including a nonrandomized retrospective design, limited sample size, and lack of data on postoperative endothelial cell counts.
MOHAMMAD ALI JAVADI, MD1 SEPEHR FEIZI, MD, MSC1 FATEMEH JAVADI, MD2 MOZHGAN REZAEI KANAVI, MD1 HASSAN GHASEMI, MD2 SETAREH KARIMDIZANI, MD1 FIROOZ MIRBABAEE, MD1 1 Ophthalmic Research Center and Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Ophthalmology, Shahed University of Medical Sciences, Tehran, Iran
Financial Disclosures: The study was financially supported by the Ophthalmic Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran.
References 1. Chen W, Lin Y, Zhang X, et al. Comparison of fresh corneal tissue versus glycerin-cryopreserved corneal tissue in deep anterior lamellar keratoplasty. Invest Ophthalmol Vis Sci 2010;51:775–81. 2. Li J, Shi S, Zhang X, et al. Comparison of different methods of glycerol preservation for deep anterior lamellar keratoplasty eligible corneas. Invest Ophthalmol Vis Sci 2012;53:5675–85. 3. Farias R, Barbosa L, Lima A, et al. Deep anterior lamellar transplant using lyophilized and Optisol corneas in patients with keratoconus. Cornea 2008;27:1030–6. 4. Li J, Yu L, Deng Z, et al. Deep anterior lamellar keratoplasty using acellular corneal tissue for prevention of allograft rejection in high-risk corneas. Am J Ophthalmol 2011;152:762–70. 5. Coombes AG, Kirwan JF, Rostron CK. Deep lamellar keratoplasty with lyophilised tissue in the management of keratoconus. Br J Ophthalmol 2001;85:788–91.
Appearance of Regressing Drusen on Adaptive Optics in Age-Related Macular Degeneration In age-related macular degeneration, material between the basal lamina of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch’s membrane are generally referred to as drusen.1 Although drusen “maturation” is characterized by accumulation of several layers of coiled membranous debris between the RPE and Bruch’s membrane,2 in drusen regression there is evidence not only of reduced formation of membranous debris, but also of its removal by macrophage. Material not removed develops calcification.2 Using tracked spectral-domain optical coherence tomographyd matched with regressing calcific drusen visualized as yellow-gray deposits with refractile areas on en face confocal scanning laser ophthalmoscope infrared (IR) or MultiColor imagesdwe recently described a laminar/multilaminar sub-RPE intense hyperreflectivity,
which we interpreted as layers of lipid mineralization, internal and external to the basement membrane, with different degrees of fragmentation.3 Adaptive optics (AO) fundus imaging allows an order of magnitude improvement of the lateral resolution of retinal images as compared with conventional en face imaging.4 We investigated en face AO imaging features of regressing drusen in 16 eyes of 12 consecutive patients (9 women; mean age 80.69.3 years). Flood illumination AO IR fundus images were obtained using an AO retinal camera (rtx1; Imagine Eyes, Orsay, France) that was previously decribed.5 In 9 of 16 eyes, en face AO IR imaging showed fused round or pisciform highly refractile lesions in correspondence of the spectral-domain optical coherence tomography featured laminar/ multilaminar sub-RPE intense hyperreflectivity (Fig 1; available at http://aaojournal.org). This could be interpreted as the in vivo visualization of mounds of membranous debris developing calcification, which, close to areas of atrophy, seem to be fused.2 Interestingly, in 7 of 16 eyes showing gray deposits with less refractile areas on en face confocal scanning laser ophthalmoscope IR imaging, the corresponding en face AO IR imaging revealed highly refractile interspersed tiny dots rather than fused round or pisciform, highly refractile lesions. In these eyes, the corresponding spectral-domain optical coherence tomography scans showed absence of laminar/multilaminar sub-RPE intense hyperreflectivity (Fig 2; available at http://aaojournal.org). This could be interpreted as the in vivo visualization of a further fragmentation and dispersion of the calcific material in advanced stages of regressing drusen. In conclusion, en face AO IR imaging allows us to distinguish fused, round or pisciform, highly refractile lesions, and highly refractile interspersed tiny dots as the characteristics of regressing drusen, possibly representing different stages in drusen calcification and regression.
GIUSEPPE QUERQUES, MD, PHD CYNTHIA KAMAMI-LEVY, MD ANOUK GEORGES, MD ALEXANDRE PEDINIELLI, MD ERIC H. SOUIED, MD, PHD Department of Ophthalmology, Centre Hospitalier Intercommunal de Creteil University Paris Est Creteil, Creteil, France
References 1. Spaide RF, Armstrong D, Browne R. Continuing medical education review: choroidal neovascularization in age-related macular degenerationewhat is the cause? Retina 2003;23: 595–614. 2. Sarks JP, Sarks SH, Killingsworth MC. Evolution of geographic atrophy of the retinal pigment epithelium. Eye 1988;2:552–77. 3. Querques G, Georges A, Ben Moussa N, et al. Appearance of regressing drusen on optical coherence tomography in age-related macular degeneration. Ophthalmology 2014;121: 173–9. 4. Liang J, Williams DR, Miller DT. Supernormal vision and highresolution retinal imaging through adaptive optics. J Opt Soc Am 1997;14:2884–92.
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