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October consultation #4
1360
CONSULTATION SECTION: CORNEA
second DSAEK procedure because tissue was discarded. Histology with CMV antibody immunohistochemistry on the excised corneal lenticule must be performed,6 and aqueous and tissue should be examined for CMV DNA by PCR assay, which has a sensitivity and specificity greater than 95%.1 I would consult with virology to assess for other viral involvement and for the possibility of coinfection with human herpesvirus-6. Coin-shaped endothelial lesions have been described clinically (and might appear in the figures) and on optical coherence tomography and owl’s-eye cells on confocal microscopy. The latter can be used to monitor postoperative progress, in particular because recurrence after PKP has been described. A perforation has occurred; thus, a fullthickness graft is necessary and can be facilitated by the technique of intraocular contact lens tamponade.7 Although systemic and/or topical valganciclovir and ganciclovir are considered the mainstays of CMV endotheliitis treatment1 and could be started immediately, no established treatment regimen exists and there might be high recurrence rates after discontinuing the antiviral treatment. Furthermore, the need for steroid use after transplantation increases the risk for CMV recurrence despite antiviral cover,1 necessitating long-term antiviral therapy. This can be accompanied by a risk for myelosuppression associated with systemic treatment and cost issues.1 It is interesting that a calcineurin inhibitor, tacrolimus, was used because another drug of this class, cyclosporine, has been associated with CMV-related anterior uveitis.8 I would not use brimonidine2 to control IOP or topical prostaglandin analogs because they have been associated with CMV-related anterior uveitis in immunocompetent individuals. Instead, I would consider systemic or topical acetazolamide initially, if tolerated. If PKP fails, I would suggest a Boston keratoprosthesis as a potential alternative.6 In the longer term, glaucoma can be a frequent and severe complication with limited medical treatment options. Microstenting could be considered, although if CMV is implicated, suprachoroidal drainage should be avoided.
REFERENCES
pez E, Chan E. Descemet stripping automated endothelial ker1. Fernandez Lo atoplasty outcomes in patients with cytomegalovirus endotheliitis. Cornea 2017; 36:108–112 2. Beltz J, Zamir E. Brimonidine induced anterior uveitis. Ocul Immunol Inflamm 2016; 24:128–133 3. Price MO, Thompson RW Jr, Price FW Jr. Risk factors for various causes of failure in initial corneal grafts. Arch Ophthalmol 2003; 121:1087–1092 4. Kandori M, Inoue T, Takamatsu F, Kojima Y, Hori Y, Maeda N, Tano Y. Prevalence and features of keratitis with quantitative polymerase chain reaction positive for cytomegalovirus. Ophthalmology 2010; 117:216–222 5. Cheung AY, Govil A, Friedstrom SR, Holland EJ. Probable donor-derived cytomegalovirus disease after keratolimbal allograft transplantation. Cornea 2017; 36:1006–1008 6. Chan ASY, Mehta JS, Al Jajeh I, Iqbal J, Anshu A, Tan DTH. Histological features of cytomegalovirus-related corneal graft infections, its associated features and clinical significance. Br J Ophthalmol 2016; 100:601–606 7. Kaines A, Versace P, Banerjee G, Coroneo M. Intraocular contact lens tamponade to facilitate penetrating keratoplasty in perforated corneas. J Cataract Refract Surg 2005; 31:876–878 8. Siak J, Chee S-P. Cytomegalovirus anterior uveitis following topical cyclosporine A.. Ocul Immunol Inflamm 2017 Apr 27; 1–4
Volume 43 Issue 10 October 2017
Natalie Afshari, MD La Jolla, California, USA My differential diagnoses include graft rejection or a viral infection such as HSV or CMV. The patient had multiple episodes of keratic precipitates in the left eye. This makes it less likely to be graft rejection and more likely to be a viral infection. The first episode occurred more than 1 year after the initial DSAEK surgery while the patient was using topical steroids once daily, and the symptoms improved with increased frequency of steroids. Four months later, many keratic precipitates and elevated IOP were noted. High IOP has been reported to be associated with herpetic endotheliitis, albeit less so with nonviral endotheliitis after keratoplasty.1 The patient had a repeat DSAEK, and the graft was clear for approximately 6 months. This was followed by another episode of keratic precipitates; however, this time, after a course of sub-Tenon triamcinolone injections, there was no clinical improvement. Then, the patient had DMEK surgery, which also resulted in keratic precipitates and ultimately corneal perforation. It is unusual to have a graft rejection so many times unless the patient’s immune system is stimulated (possibly by vaccinations). That the patient had large keratic precipitates adds to the higher likelihood of CMV infection. The prevalence of CMV infection in post-PKP patients who develop corneal stromal edema with keratic precipitates is high.2 For testing, I suggest a PCR assay of the anterior chamber fluid to assess for HSV-1, CMV, or VZV DNA. I would also consider a blood workup because specific serology for these viruses’ immunoglobulin G (IgG) and immunoglobulin M can be helpful. If the CMV IgG is negative, there is no reason to consider ganciclovir. If the perforation is small, I would glue the cornea as a temporary measure while awaiting the PCR results. If the perforation is large, a tectonic graft is indicated. The patient can be given acyclovir, and a tissue sample around the perforation can be sent for histopathologic and microbiologic assessments. If the testing reveals CMV, ganciclovir can be used for treatment. REFERENCES
1. Morishige N, Morita Y, Yamada N, Sonoda K-H. Differential changes in intraocular pressure and corneal manifestations in individuals with viral endotheliitis after keratoplasty. Cornea 2016; 35:602–606 2. Chee S-P, Jap A, Ling ECW, Ti S-E. Cytomegalovirus-positive corneal stromal edema with keratic precipitates after penetrating keratoplasty: a casecontrol study. Cornea 2013; 32:1094–1098
Farid Karimian, MD Tehran, Iran There are some points that should be considered in this case, and they can be helpful toward further management of this patient. First, the sex and age at presentation should
CONSULTATION SECTION: CORNEA
second DSAEK procedure because tissue was discarded. Histology with CMV antibody immunohistochemistry on the excised corneal lenticule must be performed,6 and aqueous and tissue should be examined for CMV DNA by PCR assay, which has a sensitivity and specificity greater than 95%.1 I would consult with virology to assess for other viral involvement and for the possibility of coinfection with human herpesvirus-6. Coin-shaped endothelial lesions have been described clinically (and might appear in the figures) and on optical coherence tomography and owl’s-eye cells on confocal microscopy. The latter can be used to monitor postoperative progress, in particular because recurrence after PKP has been described. A perforation has occurred; thus, a fullthickness graft is necessary and can be facilitated by the technique of intraocular contact lens tamponade.7 Although systemic and/or topical valganciclovir and ganciclovir are considered the mainstays of CMV endotheliitis treatment1 and could be started immediately, no established treatment regimen exists and there might be high recurrence rates after discontinuing the antiviral treatment. Furthermore, the need for steroid use after transplantation increases the risk for CMV recurrence despite antiviral cover,1 necessitating long-term antiviral therapy. This can be accompanied by a risk for myelosuppression associated with systemic treatment and cost issues.1 It is interesting that a calcineurin inhibitor, tacrolimus, was used because another drug of this class, cyclosporine, has been associated with CMV-related anterior uveitis.8 I would not use brimonidine2 to control IOP or topical prostaglandin analogs because they have been associated with CMV-related anterior uveitis in immunocompetent individuals. Instead, I would consider systemic or topical acetazolamide initially, if tolerated. If PKP fails, I would suggest a Boston keratoprosthesis as a potential alternative.6 In the longer term, glaucoma can be a frequent and severe complication with limited medical treatment options. Microstenting could be considered, although if CMV is implicated, suprachoroidal drainage should be avoided.
REFERENCES
pez E, Chan E. Descemet stripping automated endothelial ker1. Fernandez Lo atoplasty outcomes in patients with cytomegalovirus endotheliitis. Cornea 2017; 36:108–112 2. Beltz J, Zamir E. Brimonidine induced anterior uveitis. Ocul Immunol Inflamm 2016; 24:128–133 3. Price MO, Thompson RW Jr, Price FW Jr. Risk factors for various causes of failure in initial corneal grafts. Arch Ophthalmol 2003; 121:1087–1092 4. Kandori M, Inoue T, Takamatsu F, Kojima Y, Hori Y, Maeda N, Tano Y. Prevalence and features of keratitis with quantitative polymerase chain reaction positive for cytomegalovirus. Ophthalmology 2010; 117:216–222 5. Cheung AY, Govil A, Friedstrom SR, Holland EJ. Probable donor-derived cytomegalovirus disease after keratolimbal allograft transplantation. Cornea 2017; 36:1006–1008 6. Chan ASY, Mehta JS, Al Jajeh I, Iqbal J, Anshu A, Tan DTH. Histological features of cytomegalovirus-related corneal graft infections, its associated features and clinical significance. Br J Ophthalmol 2016; 100:601–606 7. Kaines A, Versace P, Banerjee G, Coroneo M. Intraocular contact lens tamponade to facilitate penetrating keratoplasty in perforated corneas. J Cataract Refract Surg 2005; 31:876–878 8. Siak J, Chee S-P. Cytomegalovirus anterior uveitis following topical cyclosporine A.. Ocul Immunol Inflamm 2017 Apr 27; 1–4
Volume 43 Issue 10 October 2017
Natalie Afshari, MD La Jolla, California, USA My differential diagnoses include graft rejection or a viral infection such as HSV or CMV. The patient had multiple episodes of keratic precipitates in the left eye. This makes it less likely to be graft rejection and more likely to be a viral infection. The first episode occurred more than 1 year after the initial DSAEK surgery while the patient was using topical steroids once daily, and the symptoms improved with increased frequency of steroids. Four months later, many keratic precipitates and elevated IOP were noted. High IOP has been reported to be associated with herpetic endotheliitis, albeit less so with nonviral endotheliitis after keratoplasty.1 The patient had a repeat DSAEK, and the graft was clear for approximately 6 months. This was followed by another episode of keratic precipitates; however, this time, after a course of sub-Tenon triamcinolone injections, there was no clinical improvement. Then, the patient had DMEK surgery, which also resulted in keratic precipitates and ultimately corneal perforation. It is unusual to have a graft rejection so many times unless the patient’s immune system is stimulated (possibly by vaccinations). That the patient had large keratic precipitates adds to the higher likelihood of CMV infection. The prevalence of CMV infection in post-PKP patients who develop corneal stromal edema with keratic precipitates is high.2 For testing, I suggest a PCR assay of the anterior chamber fluid to assess for HSV-1, CMV, or VZV DNA. I would also consider a blood workup because specific serology for these viruses’ immunoglobulin G (IgG) and immunoglobulin M can be helpful. If the CMV IgG is negative, there is no reason to consider ganciclovir. If the perforation is small, I would glue the cornea as a temporary measure while awaiting the PCR results. If the perforation is large, a tectonic graft is indicated. The patient can be given acyclovir, and a tissue sample around the perforation can be sent for histopathologic and microbiologic assessments. If the testing reveals CMV, ganciclovir can be used for treatment. REFERENCES
1. Morishige N, Morita Y, Yamada N, Sonoda K-H. Differential changes in intraocular pressure and corneal manifestations in individuals with viral endotheliitis after keratoplasty. Cornea 2016; 35:602–606 2. Chee S-P, Jap A, Ling ECW, Ti S-E. Cytomegalovirus-positive corneal stromal edema with keratic precipitates after penetrating keratoplasty: a casecontrol study. Cornea 2013; 32:1094–1098
Farid Karimian, MD Tehran, Iran There are some points that should be considered in this case, and they can be helpful toward further management of this patient. First, the sex and age at presentation should