Objective To evaluate the clinical features of and histologic findings from failed Descemet stripping automated endothelial keratoplasty (DSAEK). Methods This retrospective observational case series evaluated 47 consecutive corneal specimens from 42 patients who underwent either penetrating keratoplasty or repeated DSAEK for failed DSAEK. Clinical information was obtained for the cases. Sections of the specimens were examined using light microscopy. Immunohistochemical staining was performed for cytokeratins AE1/AE3 and for the myogenic marker smooth-muscle actin when indicated. Transmission electron microscopic examination was performed in some cases. Results Graft survival ranged from 0.5 to 34 months. Histologic examination showed that 94% of the specimens (44 of 47) had endothelial cell loss. Residual host Descemet membrane (19%; 9 of 47), fibrocellular tissue (19%; 9 of 47), epithelial implantation (15%; 7 of 47), and fungal infection (4%; 2 of 47) were also identified. Immunohistochemical stains were positive for AE1/AE3 in the epithelial implantations and for smooth-muscle actin in cells in the fibrocellular proliferations. Conclusions The principal cause of failed DSAEK is endothelial cell loss. Residual host Descemet membrane, fibrocellular tissue at the edge of the lenticule, and epithelial implantation are common histologic findings. Fungal infection may occur in the setting of DSAEK.

PURPOSE. To compare the efficacy of microneedle-delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con1 versus vehicle controls on choroidal neovascularization (CNV) growth in a pig model. METHODS. Forty-one pigs were injected on the day of CNV induction (hI-con1 on postinduction day 14) with either 2.5 mg Ivit bevacizumab (n = 9), 1 mg Ivit pazopanib (n = 9), 300 Ivit μg hI-con1 (n = 4), or 1 mg SC pazopanib (n = 9), vs. 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at week 2 (11), 3 (8), 4 (11), and 8 (11), and eyes were fixed for histology. The size of the CNV was determined from histology, and CNV height was the primary outcome measure. Immunostaining for cytotoxic T-cells was performed in the hI-con1 study. RESULTS. In 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost during dissection. One animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller mean height measurements (90 ± 20 μm) versus controls (180 ± 20 μm; P = 0.009), and Ivit pazopanib had smaller maximum CNV height (173 ± 43 μm) compared to SC pazopanib (478 ± 105 μm; P = 0.018). The mean lesion size in hI-con1–treated animals trended smaller than in controls (P = 0.11). Immunostaining did not detect cytotoxic T-cells. CONCLUSIONS. Intravitreal pazopanib and to a lesser extent hI-con1 reduced the size of CNV lesions. The pig model has nearly a 100% rate of type 2 CNV induction and is a reliable preclinical model with pharmacodynamics similar to humans.

Uveal melanoma (UM) is the most prevalent primary intraocular malignancy in adults, and patients that develop metastases (~50%) survive <1 year, highlighting the urgent need for new therapies. TCGA has recently revealed that a hypoxia gene signature is associated with poor UM patient prognosis. Here we show that expression of hypoxia-regulated collagen prolyl-4-hydroxylase genes P4HA1 and P4HA2 is significantly upregulated in UM patients with metastatic disease and correlates with poor prognosis, suggesting these enzymes might be key tumor drivers. We targeted hypoxia-induced expression of P4HA1/2 in UM with KCN1, a hypoxia inducible factor-1 (HIF-1) pathway inhibitor and found potent inhibition of primary and metastatic disease and extension of animal survival, without overt side effects. At the molecular level, KCN1 antagonized hypoxia-induced expression of P4HA1 and P4HA2, which regulate collagen maturation and deposition in the extracellular matrix. The treatment decreased prolyl hydroxylation, induced proteolytic cleavage and rendered a disordered structure to collagen VI, the main collagen produced by UM, and reduced UM cell invasion. Together, these data demonstrate that extracellular collagen matrix formation can be targeted in UM by inhibiting hypoxia-induced P4HA1 and P4HA2 expression, warranting further development of this strategy in patients with uveal melanoma.

Background: Intraocular lymphoma accounts for fewer than 1% of intraocular tumors. When the posterior segment is involved, it can be further classified as vitreoretinal or choroidal lymphoma. Vitreoretinal lymphoma (VRL) can rarely masquerade as an infectious retinitis making diagnosis and management challenging. Results: A 73-year-old woman with a history of non-central nervous system (CNS) involving diffuse large B-cell lymphoma (DLBCL) was referred for worsening blurry vision—visual acuity of count figures at 2 ft—in her right eye for 8 months. Dilated fundus examination of the right eye was significant for retinal whitening and dot-blot hemorrhages, which was concerning for a viral retinitis and guided initial management. Secondary intraocular lymphoma was also considered. The retinal disease continued to progress despite intravitreal and systemic antiviral therapy, and a diagnostic vitrectomy was inconclusive. A retinal biopsy was then performed, which showed DLBCL, confirming a diagnosis of secondary VRL. Three subsequent treatments with intravitreal methotrexate led to regression of the VRL. Conclusions: Our case highlights the utility of a retinal biopsy after an inconclusive diagnostic vitrectomy in a challenging scenario of VRL to establish a diagnosis and initiate successful treatment. A multidisciplinary team of providers was essential for diagnosis, comprehensive workup, medical and surgical management of the patient.

Purpose: The purpose of this study is to report a case of microsporidial endophthalmitis after penetrating keratoplasty in a healthy patient and discuss the management. Methods: This is a case report. Results: A 69-year-old healthy male underwent penetrating keratoplasty for corneal scar secondary to herpes stromal keratitis. He presented with features of acute graft rejection 3 years later. After failure of medical management, a repeat full thickness keratoplasty was performed. Pathologic examination of the corneal specimen showed microsporidia. The patient then developed a chronic endophthalmitis, and a vitreous tap and injection followed by pars plana vitrectomy were performed. Pathologic examination of tissue showed microsporidia. Conclusions: Microsporidia are being increasingly identified as the cause of stromal keratitis. This is the first report of microsporidial endophthalmitis in a patient without underlying systemic illness.

A 47-year-old woman required penetrating keratoplasty in the right eye after developing delayed visually significant corneal scarring bilaterally after laser in situ keratomileusis (LASIK) in 1997 following epikeratoplasty in 1987. Spectral domain ocular coherence tomography of the left cornea showed a 100 μm lenticule with a LASIK flap posterior to the host Bowman layer at 250 μm. Histopathology and electron microscopy of the right corneal button showed a 120 μm lenticule with a LASIK flap within the lenticule at 100 μm. Clinically significant scarring was present within the LASIK flap interface, within the lenticule stroma, and within the area of the underlying host Bowman layer. There were keratocytes at the junction between the LASIK flap and lenticule stromal bed. Although epikeratoplasty is no longer practiced, post-epikeratoplasty patients may present for refractive surgical options and LASIK carries significant risks for corneal scarring in these individuals, especially when using flap-creating devices that may create thin LASIK flaps.

Scleritis is a potentially sight-threatening inflammatory condition of the sclera that may be associated with keratitis, uveitis, glaucoma, and exudative retinal detachments. Sinus histiocytosis with massive lymphadenopathy, or Rosai-Dorfman disease, is a rare histiocytic disorder characterized by massive, painless lymphadenopathy. While extranodal involvement is common, eye involvement is infrequent and most often seen in the orbit or eyelid. Direct ocular involvement is exceedingly rare. We report a case of Rosai-Dorfman disease that simulated nodular scleritis and panuveitis.

Over the past decade, chemoreduction has become the treatment of choice for the initial management of retinoblastoma. Yet despite its established use, chemoreduction has not been able to treat diffuse infiltrating retinoblastoma, the least common subtype of retinoblastoma. Herein we report two cases in which residual intraretinal retinoblastoma exhibiting flat and diffuse infiltration was found on pathological exam after a chemoreduction failure. The chemoreduction reduced some of the tumor and unmasked the intraretinal component.

This article describes 2 unusual cases of osseous metaplasia occurring within the eyelid and presents a brief review of the literature on cutaneous calcification. A 62-year-old man sought treatment for an eyelid mass containing osseous metaplasia in an area of lymphoid hyperplasia. An extensive oncologic workup ruled out malignancy. A 46-year-old man with a history of recurrent chalazion sought treatment for a firm mass of the upper eyelid that demonstrated bone formation in an area of sebaceous glands. Both lesions were excised with no further recurrence. Osseous metaplasia of the eyelid is a rare entity with diverse etiologies ranging from congenital syndromes to trauma, neoplasm, and inflammation. In some cases, a precise etiology cannot be identified.

The central vision-threatening event in glaucoma is dysfunction and loss of retinal ganglion cells (RGCs), thought to be promoted by local tissue deformations. Here, we sought to reduce tissue deformation near the optic nerve head by selectively stiffening the peripapillary sclera, i.e. the scleral region immediately adjacent to the optic nerve head. Previous scleral stiffening studies to treat glaucoma or myopia have used either pan-scleral stiffening (not regionally selective) or regionally selective stiffening with limited access to the posterior globe. We present a method for selectively stiffening the peripapillary sclera using a transpupillary annular light beam to activate methylene blue administered by retrobulbar injection. Unlike prior approaches to photocrosslinking in the eye, this approach avoids the damaging effects of ultraviolet light by employing red light. This targeted photocrosslinking approach successfully stiffened the peripapillary sclera at 6 weeks post-treatment, as measured by whole globe inflation testing. Specifically, strain was reduced by 47% when comparing treated vs. untreated sclera within the same eye (n = 7, p=0.0064) and by 54% when comparing the peripapillary sclera of treated vs. untreated eyes (n = 7, p<0.0001). Post-treatment characterization of RGCs (optic nerve axon counts/density, and grading), retinal function (electroretinography), and retinal histology revealed that photocrosslinking was associated with some ocular toxicity. We conclude that a transpupillary photocrosslinking approach enables selective scleral stiffening targeted to the peripapillary region that may be useful in future treatments of glaucoma.