Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept.

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Advanced Glycation End-Products and Diabetic Neuropathy of the Retina.

Diabetic retinopathy is a tissue-specific neurovascular impairment of the retina in patients with both type 1 and type 2 diabetes. Several pathological factors are involved in the progressive impairment of the interdependence between cells that consist of the neurovascular units (NVUs). The advanced glycation end-products (AGEs) are one of the major pathological factors that cause the impairments of neurovascular coupling in diabetic retinopathy. Although the exact mechanisms for the toxicities of the AGEs in diabetic retinopathy have not been definitively determined, the AGE-receptor of the AGE (RAGE) axis, production of reactive oxygen species, inflammatory reactions, and the activation of the cell death pathways are associated with the impairment of the NVUs in diabetic retinopathy. More specifically, neuronal cell death is an irreversible change that is directly associated with vision reduction in diabetic patients. Thus, neuroprotective therapies must be established for diabetic retinopathy. The AGEs are one of the therapeutic targets to examine to ameliorate the pathological changes in the NVUs in diabetic retinopathy. This review focuses on the basic and pathological findings of AGE-induced neurovascular abnormalities and the potential therapeutic approaches, including the use of anti-glycated drugs to protect the AGE-induced impairments of the NVUs in diabetic retinopathy.

Neurovascular Cell Death and Therapeutic Strategies for Diabetic Retinopathy.

Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness worldwide. DR was recently defined as a neurovascular disease associated with tissue-specific neurovascular impairment of the retina in patients with diabetes. Neurovascular cell death is the main cause of neurovascular impairment in DR. Thus, neurovascular cell protection is a potential therapy for preventing the progression of DR. Growing evidence indicates that a variety of cell death pathways, such as apoptosis, necroptosis, ferroptosis, and pyroptosis, are associated with neurovascular cell death in DR. These forms of regulated cell death may serve as therapeutic targets for ameliorating the pathogenesis of DR. This review focuses on these cell death mechanisms and describes potential therapies for the treatment of DR that protect against neurovascular cell death.

Diabetic Neuropathy of the Retina and Inflammation: Perspectives.

A clear connection exists between diabetes and atherosclerotic cardiovascular disease. Consequently, therapeutic approaches that target both diseases are needed. Clinical trials are currently underway to explore the roles of obesity, adipose tissue, gut microbiota, and pancreatic beta cell function in diabetes. Inflammation plays a key role in diabetes pathophysiology and associated metabolic disorders; thus, interest has increased in targeting inflammation to prevent and control diabetes. Diabetic retinopathy is known as a neurodegenerative and vascular disease that occurs after some years of poorly controlled diabetes. However, increasing evidence points to inflammation as a key figure in diabetes-associated retinal complications. Interconnected molecular pathways, such as oxidative stress, and the formation of advanced glycation end-products, are known to contribute to the inflammatory response. This review describes the possible mechanisms of the metabolic changes in diabetes that involve inflammatory pathways.

Optical coherence tomography findings in three patients with Werner syndrome.

BACKGROUND: Werner syndrome is a rare, autosomal recessive disorder characterised by premature aging. It is a typical hereditary progeroid syndrome that can be difficult to diagnose owing to its rarity and the similarity of some of its symptoms, such as juvenile cataracts, to other common ophthalmologic conditions. Early onset of bilateral cataracts is currently used as the ophthalmological feature for Werner syndrome; however, ophthalmologists often find performing a detailed examination of the medical history and genetic testing for Werner syndrome at the time of an ophthalmologic consultation challenging. If a unique ocular finding was observed on ocular examinations in cases of juvenile bilateral cataracts, we could consider Werner syndrome as a differential diagnosis.  CASE PRESENTATION: We documented the cases of three patients with Werner syndrome in whom thinning of the retina in the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were observed using optical coherence tomography (OCT). Visual field tests revealed the loss of visual field mainly owing to glaucoma. The thinnig of the choroidal thickness (CT) in three patients was also observed using enhanced depth imaging (EDI)-OCT. CONCLUSIONS: Three patients have thinning of the RNFL, GCC, and choroidal thickness and the loss of visual field. These findings suggest the need for including Werner syndrome in the differential diagnosis when patients presenting with juvenile cataracts of unknown cause also show abnormal retinal and choroidal thinning in the OCT images.

Ten-year epidemiological study of ocular and orbital tumors in Chiba University Hospital.

BACKGROUND: The purpose of this study is to determine the epidemiology of tumors of the ocular adnexa and orbit in Japan. METHODS: We conducted a retrospective study on the histopathological reports in the medical records of the Chiba University Hospital from April 2009 to March 2019. Three hundred and seventy two records were examined. In addition, we examined the annual changes in the major types of tumors including malignant lymphomas and IgG4-related diseases (IgG4-RDs). RESULTS: There were 270 conjunctival or eyelid tumors with 166 benign and 104 malignant. There were 102 orbital tumors with 55 benign, 47 malignant tumors, and 21 cases of IgG4-RDs. Ten cases of adenoma (2.7%), another benign tumor, was also diagnosed. The major malignant tumors were malignant lymphoma in 74 cases, sebaceous gland carcinoma (SGC) in 28 cases, basal cell carcinoma in 15 cases, and squamous cell carcinoma in 8 cases. The SGCs were the most common malignant eyelid tumor at 54%. Among the malignant lymphomas, extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue type, MALT lymphomas, was the most common at 51 cases and the second most common was the diffuse large B-cell lymphoma at 11 cases. The ratio of MALT lymphomas to that of all malignant lymphomas increased significantly with years. The serum IgG4 values were measured more often in the last 5 years (70%) than in the former 5 years (33%). CONCLUSIONS: We conclude that malignant lymphoma is a major malignant tumor in Japan and pathological biopsies should be done proactively to prevent missing IgG4-positive MALT lymphomas.

The Pathogenesis and Therapeutic Approaches of Diabetic Neuropathy in the Retina.

Diabetic retinopathy is a major retinal disease and a leading cause of blindness in the world. Diabetic retinopathy is a neurovascular disease that is associated with disturbances of the interdependent relationship of cells composed of the neurovascular units, i.e., neurons, glial cells, and vascular cells. An impairment of these neurovascular units causes both neuronal and vascular abnormalities in diabetic retinopathy. More specifically, neuronal abnormalities including neuronal cell death and axon degeneration are irreversible changes that are directly related to the vision reduction in diabetic patients. Thus, establishment of neuroprotective and regenerative therapies for diabetic neuropathy in the retina is an emergent task for preventing the blindness of patients with diabetic retinopathy. This review focuses on the pathogenesis of the neuronal abnormalities in diabetic retina including glial abnormalities, neuronal cell death, and axon degeneration. The possible molecular cell death pathways and intrinsic survival and regenerative pathways are also described. In addition, therapeutic approaches for diabetic neuropathy in the retina both in vitro and in vivo are presented. This review should be helpful for providing clues to overcome the barriers for establishing neuroprotection and regeneration of diabetic neuropathy in the retina.

REGIONAL DENSITIES OF RETINAL CAPILLARIES AND RETINAL SENSITIVITIES AFTER MACULAR HOLE SURGERY WITH INTERNAL LIMITING MEMBRANE PEELING.

PURPOSE: To measure the vascular density (VD) of the retinal capillary plexuses by optical coherence tomography angiography (OCTA) after surgery for an idiopathic macular hole. METHODS: Retrospective, observational case series.Sixteen eyes of 16 patients with an idiopathic macular hole underwent vitrectomy with internal limiting membrane peeling. The VDs of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were determined by OCTA, and the retinal sensitivity (RS) and the inner retinal thickness (IRT) were measured before, and at 3, 6, and 12 months after the surgery. The VD, RS, and IRT were measured at the four parafoveal quadrants. RESULTS: The mean age was 68.9 years. The VDs of the SCP and DCP were significantly correlated with the RS and IRT at 12 months postoperatively (all P < 0.001 for both SCP and DCP). The VDs of the SCP and DCP were higher, the RS more sensitive, and the IRT thicker in the nasal than the temporal quadrant at 12 months (P < 0.001, <0.001, =0.009, <0.001, respectively). CONCLUSION: The significant correlation between the VDs of the SCP and DCP and the RS and IRT may be due to the nasal shift of the posterior retina.

Comparison of the Efficacy of Sub-Tenon versus Intravitreal Triamcinolone Acetonide Injection during Cataract Surgery for Diabetic Macular Edema.

PURPOSE: We compared the efficacy of sub-Tenon triamcinolone acetonide (STTA) to intravitreal triamcinolone aceto-nide (IVTA) injections during cataract surgery (CS) for patients with diabetic macular edema (DME). METHODS: The medical records of 33 eyes (26 patients) with DME which had undergone CS with STTA were compared to those of 34 eyes (27 patients) with DME which had undergone CS with IVTA. Central foveal thickness and best-corrected visual acuity (BCVA) were measured at the baseline and 1, 3, and 6 months after the surgery. RESULTS: The BCVAs after STTA and IVTA were significantly improved at 3 and 6 months. Thirteen eyes in the IVTA group and 21 eyes in the STTA group required other therapies (p < 0.05). One case developed intraocular pressure elevation after IVTA and underwent selective la ser trabeculoplasty. CONCLUSIONS: Ophthalmologists should consider the merits and demerits of IVTA and STTA for DME treatment after CS.

The Case of IgG4-related Ophthalmic Disease Accompanied by Compressive Optic Neuropathy.

A 76-year-old woman was diagnosed with thyroid-associated orbitopathy (TAO) associated with hypothyroidism at another clinic. Magnetic resonance imaging showed enlargements of the extraocular muscles. Because her best-corrected visual acuity (BCVA) was 0.01OD, she was referred to the Chiba University Hospital. She had an elevation of serum IgG4. She was diagnosed with possible IgG4-related ophthalmic disease (IgG4-ROD) accompanied by optic nerve compression with the mass. She underwent methylprednisolone pulse therapy, and, two months later, her BCVA and visual field defect were greatly improved. Our findings indicate that ophthalmologists should be aware that IgG4-ROD can be masked by lesions associated with TAO.

The Case of IgG4-Related Ophthalmic Disease with Perivascular Lesions of Superior Ophthalmic Vein Associated with Optic Nerve Disturbance.

A 61-year-old man with hyperthyroidism had exophthalmos with dilated conjunctival vessels in both eyes. Magnetic resonance imaging showed that the superior ophthalmic veins had a funicular-like appearance. Cerebral angiography showed no blood flow from both internal carotid arteries to the cavernous sinus, thus excluding a carotid-cavernous fistula. Blood tests showed an elevation of IgG4 (281 mg/dl), and a IgG4-related ophthalmic disease was considered. Steroid pulse therapy was performed, and all of the abnormal findings were improved. We concluded that this was a rare case of IgG4-related ophthalmic disease with perivascular lesions of the superior ophthalmic vein associated with optic nerve disturbance.

Reduction of Optic Disc Oedema by Bortezomib and Dexamethasone Followed by Autologous Peripheral Blood Stem Cell Transplantation in Patient with POEMS Syndrome.

The authors present findings in a 39-year-old man with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome with bilateral optic disc oedema. He was successfully treated with bortezomib and dexamethasone followed by autologous peripheral blood stem cell transplantation. The peripapillary retinal thickness was reduced in the optical coherence tomographic (OCT) images along with a decrease of the serum vascular endothelial growth factor (VEGF) levels. The authors recommend OCT to monitor the changes in the signs of POEMS syndrome after treatments.

CORRELATIONS BETWEEN PREOPERATIVE RETINAL PIGMENT EPITHELIAL PROTRUSIONS AND POSTOPERATIVE OUTCOMES IN EYES WITH IDIOPATHIC MACULAR HOLES.

BACKGROUND/PURPOSE: To determine the relationship between the alterations in the preoperative morphology of the retinal pigment epithelium (RPE) and the postoperative recovery after surgery to close an idiopathic macular hole (MH). METHODS: Retrospective interventional case series. Fifty-nine eyes of 59 patients with an idiopathic MH were studied. Pars plana vitrectomy was performed with the removal of the internal limiting membrane. The best-corrected visual acuity was measured, and the retinal morphology, including the presence of small RPE protrusions at the bottom of MH, was determined by spectral domain optical coherence tomography before and at 1, 3, and 6 months postoperatively. RESULTS: The mean age of the patients was 66.7 years. Forty eyes (68%) had preoperative alterations of the RPE. The minimal (P < 0.001) and the base (P < 0.001) diameters of the MH were significantly larger in eyes with preoperative RPE alterations. The best-corrected visual acuity was significantly worse at baseline (P = 0.014) and at 6 months postoperatively (P = 0.048) in the eyes with RPE alterations. The defect of the ellipsoid zone was significantly longer in eyes with baseline RPE alterations at 1, 3, and 6 months postoperatively (P < 0.001, P = 0.001, and P = 0.032). CONCLUSION: The presence of RPE protrusions at baseline was significantly correlated with slower morphologic recovery and poorer visual acuity after MH closure.

SUPERFICIAL FOVEAL AVASCULAR ZONE DETERMINED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY BEFORE AND AFTER MACULAR HOLE SURGERY.

PURPOSE: To determine the size of the superficial foveal avascular zone (FAZ) by optical coherence tomography angiography before and after surgery for an idiopathic macular hole. METHODS: A retrospective, observational case series, in which 16 eyes of 16 patients with an idiopathic macular hole were studied. Pars plana vitrectomy was performed with internal limiting membrane peeling. The foveal retinal vasculature was examined by optical coherence tomography angiography, and the area of the superficial FAZ was determined before, and at 1 and 3 months after the surgery. The area of the macular hole was also measured in the en face optical coherence tomography images. The central foveal thickness was measured to determine the relationship between the size of the superficial FAZ and foveal shape. The unaffected fellow eyes were used as controls. RESULTS: The mean age of the patients was 68.9 years. The average preoperative superficial FAZ area was 0.45 ± 0.14 mm, which was significantly reduced to 0.23 ± 0.08 mm at 1 month (P < 0.001) and 0.25 ± 0.08 mm at 3 months postoperatively (P < 0.001). The size was smaller than that of the control eyes (0.36 ± 0.12 mm, P = 0.003). There was a significant inverse correlation between the area of the postoperative superficial FAZ and the central foveal thickness (r = -0.589, P = 0.016). The correlations between the visual acuity and the area of the superficial FAZ at 1 and 3 months postoperatively were not significant (P = 0.369 and 0.285). CONCLUSION: The significant decrease in the superficial FAZ after the macular hole surgery indicates that there was a centripetal movement of the foveal tissue postoperatively.

SCLERAL IMBRICATION COMBINED WITH PARS PLANA VITRECTOMY WITHOUT INTERNAL LIMITING MEMBRANE PEELING FOR MYOPIC SCHISIS.

PURPOSE: We investigated whether scleral imbrication combined with pars plana vitrectomy without internal limiting membrane peeling would be effective in treating eyes with myopic macular schisis. METHODS: In this retrospective, interventional case series, 8 eyes of 8 patients with myopic retinoschisis without a macular hole were studied. Scleral imbrication was done with 6-mm-wide mattress sutures placed at the temporal quadrants. Pars plana vitrectomy and removal of the vitreous cortex were performed, but the internal limiting membrane was not removed. The best-corrected visual acuity was measured, and the retinal morphology was determined by spectral-domain optical coherence tomography before and at 6 and 12 months postoperatively. RESULTS: The mean age of the subjects was 67.1 years. The best-corrected visual acuity improved from 0.71 ± 0.25 to 0.36 ± 0.19 logarithm of the minimum angle of resolution units (Snellen equivalent: from 20/100 to 20/50) at 12 months (P = 0.028). The axial length was shortened from 29.5 ± 1.7 to 28.5 ± 2.5 at 12 months (P = 0.012). The central foveal thickness decreased from 540 ± 171 µm to 170 ± 85 µm at 12 months (P = 0.012). In the 6 macular-detached eyes, 5 eyes (83%) had a complete resolution. The curvature of posterior eye wall was flatter at 12 months (P = 0.049). No retinal complications were observed. CONCLUSION: Scleral imbrication combined with pars plana vitrectomy can be an effective method of treating myopic schisis.

Level of vitreous alpha-B crystallin in eyes with rhegmatogenous retinal detachment.

PURPOSE: Alpha-B crystallin (αB-crystallin) is a molecular chaperone, and one of the small heat shock proteins (sHSPs). αB-crystallin has been shown to have neuroprotective properties. The purpose of this study was to determine the level of αB-crystallin in eyes with a rhegmatogenous retinal detachment (RRD). METHODS: Vitreous samples were collected before vitrectomy from 32 eyes of 32 consecutive patients with RRD. The concentration of αB-crystallin was measured by enzyme-linked immunosorbent assay (ELISA). Vitreous samples were also collected before vitrectomy from 16 patients with an idiopathic macular hole and epiretinal membrane, and used as controls. RESULTS: The mean age was 56 years (range, 31-67 years) in the RRD cases and 66 years (range, 49-77 years) in the controls. The mean level of αB-crystallin was significantly higher in the RRD cases (36.7 ± 37.4 ng/ml) than that in controls (8.5 ± 12.2 ng/ml; P = 0.0028). CONCLUSIONS: The increased level of αB-crystallin suggests that αB-crystallin may play a neuroprotective role by lessening retinal cell death after a retinal detachment.

Correlation between serum level of vascular endothelial growth factor and subfoveal choroidal thickness in patients with POEMS syndrome.

PURPOSE: The study was conducted to determine whether serum vascular endothelial growth factor (VEGF) levels are significantly correlated with subfoveal choroidal thickness (CT) and foveal thickness (FT) in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. PATIENTS AND METHODS: In this cross-sectional observational case series, we studied 31 eyes of 16 treatment-naïve patients with POEMS syndrome with no evidence of fundus abnormalities. Subfoveal CT and FT were measured using enhanced depth imaging optical coherence tomography (EDI-OCT), and correlations between serum VEGF levels and subfoveal CT and FT were determined. RESULTS: The mean subfoveal CT was 417.9 ± 73.5 µm (right eye, 416.7 ± 81.2 µm; left eye, 419.0 ± 68.1 µm), and the mean FT was 243.8 ± 35.2 µm (right eye, 248.8 ± 22.0 µm; left eye, 239.1 ± 44.6 µm). There was a significant positive correlation between the serum VEGF level and subfoveal CT (right eye, r = 0.58, p = 0.021; left eye, r = 0.60, p = 0.012), but the correlation between the level of serum VEGF and FT was not significant (right eye, r = 0.007, p > 0.05; left eye, r = 0.25, p > 0.05). CONCLUSIONS: The significant correlation between the serum VEGF level and subfoveal CT in patients with POEMS syndrome suggests that choroidal thickness is influenced by the level of serum VEGF. These results not only aid in an understanding of the pathogenesis of ocular changes in patients with POEMS syndrome, but also offer clues regarding the pathogenesis of other choroidal diseases.

Spontaneous Recovery of Neuromyelitis Optica Spectrum Disorder during Pregnancy.

Neuromyelitis optica spectrum disorder (NMO-SD) is an autoimmune inflammatory disorder associated with the anti-aquaporin-4 (AQP4) antibody. Over 90% of NMO-SD patients have poor prognosis, and pregnancy is a disease-worsening factor. The authors report the findings in a case of NMO-SD that recovered spontaneously during pregnancy. A 28-years-old woman developed optic neuritis (ON) of the right eye in the 14th week of pregnancy. Her best-correlated visual acuity (BCVA) was 0.02 OD, the critical flicker frequency (CFF) was not measurable, and the mean deviation (MD) of the Humphrey perimetry 30-2 was -42 dB. Magnetic resonance imaging (MRI; T2 short-tau inversion recovery [STIR]) showed high-intensity right optic nerve. The patient was diagnosed with NMO-SD by the detection of seropositive anti-AQP4 antibody in her serum. Corticosteroid pulse therapy was considered, but the patient declined any treatment. Two weeks later, her BCVA improved to 1.2 (OD). Nine weeks later, the MD of Humphrey perimetry 30-2 improved to -1.2 dB and the CFF was 39.8 Hz. There have been no signs of recurrence for 6 months. Spontaneously recovered cases of NMO-SD during pregnancy are very rare. Although the factors leading to good outcomes have not been identified, this case suggests that the immunological condition at the early stage of the pregnancy may have different from that at later stages. Further studies are needed to identify the relationship between pregnancy and NMO-SD.

Case of Orbital Mucosa-Associated Lymphoid Tissue Lymphoma Associated with Serous Retinal Detachment.

We present a case of orbital mucosa-associated lymphoid tissue (MALT) lymphoma accompanied by a serous retinal detachment (SRD). A 44-year-old man who developed uveitis accompanied by a SRD in the right eye was referred to the Chiba National Hospital. B-mode ultrasonography and magnetic resonance imaging (MRI) showed a thickened choroidal membrane and a retrobulbar mass. Although topical steroid treatments improved the inflammation, the SRD did not improve. He was then referred to the Chiba University Hospital. Two months later, the retrobulbar mass had increased, and a partial resection biopsy combined with flow cytometry was performed. The final diagnosis was MALT lymphoma. After R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy, signs of the tumour could not be detected and the SRD was reduced. We conclude that the SRD was most likely due to the infiltration of lymphoma cells and also to choroidal circulatory disturbances. Retrobulbar malignant lymphomas associated with a SRD are very rare and difficult to diagnosis without biopsy, but because early diagnosis is helpful in deciding the appropriate therapy, we recommend partial biopsy.

Werner syndrome with refractory cystoid macular edema and immunohistochemical analysis of WRN proteins in human retinas.

BACKGROUND: To present our findings in a case of Werner syndrome with refractory cystoid macular edema (CME) and to determine the expression and the distribution of WRN proteins in human retinas. CASE PRESENTATION: A 35-year-old man with Werner syndrome who developed CME after YAG laser treatment was studied. Optical coherence tomographic (OCT) scans were used to examine the CME in the right eye. The patient received topical eye drops (0.1% bromfenac sodium hydrate twice daily and 1% dorzolamide hydrochloride thrice daily), sub-Tenon triamcinolone injection thrice, intravitreal bevacizumab injection twice, and pars plana vitrectomy of the right eye. Genetic analyses were performed to diagnose the disease. To examine the expression and distribution of WRN proteins in the retinas, immunohistochemistry for WRN proteins was performed in human retinas. The CME in the right eye was not improved by any of the treatments. During the follow-up period, CME developed in the left eye. Genetic analyses detected compound heterozygosity, Mut4 and Mut11, in the WRN gene and the individual was diagnosed with Werner syndrome. Immunohistochemical analysis of WRN proteins expression in human retinas showed that WRN proteins were expressed in the parts of the Müller cells in the inner nuclear layer and outer nuclear layer. CONCLUSION: Patients with Werner syndrome can develop severe CME after laser treatment. A pathological link may exist between mutations in the WRN gene and the development of CME in patients with Werner syndrome.