Risk of disease transmission from flexible nasoendoscopy during the coronavirus disease 2019 pandemic.

BACKGROUND: Concerns have emerged regarding infection transmission during flexible nasoendoscopy. METHODS: Information was gathered prospectively on flexible nasoendoscopy procedures performed between March and June 2020. Patients and healthcare workers were followed up to assess for coronavirus disease 2019 development. One-sided 97.5 per cent Poisson confidence intervals were calculated for upper limits of risk where zero events were observed. RESULTS: A total of 286 patients were recruited. The most common indication for flexible nasoendoscopy was investigation of 'red flag' symptoms (67 per cent). Forty-seven patients (16 per cent, 95 per cent confidence interval = 13-21 per cent) had suspicious findings on flexible nasoendoscopy requiring further investigation. Twenty patients (7.1 per cent, 95 per cent confidence interval = 4.4-11 per cent) had new cancer diagnoses. Zero coronavirus disease 2019 infections were recorded in the 273 patients. No. 27 endoscopists (the doctors and nurses who carried out the procedures) were followed up.The risk of developing coronavirus disease 2019 after flexible nasoendoscopy was determined to be 0-1.3 per cent. CONCLUSION: The risk of coronavirus disease 2019 transmission associated with performing flexible nasoendoscopy in asymptomatic patients, while using appropriate personal protective equipment, is very low. Additional data are required to confirm these findings in the setting of further disease surges.

Presentation of the H-Y antigen on Langerhans' cell-negative corneal grafts downregulates the cytotoxic T cell response and converts responder strain mice into phenotypic nonresponders.

We have used the murine cornea is an allograft model to investigate the relative roles of graft-derived IA+ APC (Langerhans' cells) and host-derived APC during the induction of CTL responses to H-Y. The natural exclusion of LC from the immunizing corneal graft led to a specific state of unresponsiveness to H-Y in responder strain mice, while inclusion of LC resulted in responsiveness. Failure to respond to H-Y could not be attributed to the absence of H-Y or IA antigen expression on the surface of LC-deficient grafts but instead, appeared to be due to active suppression of the T helper cell response during in vivo priming. Reprocessing of the H-Y antigen by host APC did not occur after immunization with H-Y presented on H-2-incompatible grafts unless presented initially by graft-derived LC. H-2 as well as some non-H-2 alloantigens were presented to the host without a requirement for donor-derived LC. Thus there appear to be differential requirements for the processing and presentation of alloantigens.

Month-6 primary outcomes of the READ-3 study (Ranibizumab for Edema of the mAcula in Diabetes-Protocol 3 with high dose).

PURPOSE: To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME) and a central subfield thickness (CFT) of ≥250 µm on time-domain optical coherence tomography.DesignRandomized, controlled, multicenter clinical trial. METHODS: Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n=77) or 2.0 mg (n=75) RBZ. Study eyes received 6-monthly injections.Main outcome measuresThe primary outcome measure was the mean change in best corrected visual acuity (BCVA) at month 6. Secondary outcomes included the incidence and severity of systemic and ocular adverse events and the mean change in CFT from baseline. RESULTS: In all, 152 eyes (152 patients) were randomized in the study. At month 6, the mean improvement from baseline BCVA was +9.43 letters in the 0.5 mg RBZ group and +7.01 letters in the 2.0 mg RBZ group (P=0.161). At month 6, one death occurred in the 0.5 mg RBZ group and three deaths in the 2.0 mg RBZ group, all due to myocardial infarction in subjects with a prior history of heart disease. Mean CFT was reduced by 168.58 µm in the 0.5 mg RBZ group and by 159.70 µm in the 2.0 mg RBZ group (P=0.708). CONCLUSIONS: There was no statistically significant difference in the mean number of letters gained between the 0.5 and 2.0 mg RBZ groups through month 6. In this DME study population, high-dose RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

Evidence that the fate of class II-disparate corneal grafts is determined by the timing of class II expression.

While the immune privilege nature of the eye affords significant protection to corneal grafts, immunologic rejection is the leading cause of graft failure. Class II antigens are normally absent or expressed at very low levels in normal cornea. The role that class II antigens play in causing graft rejection is particularly interesting. Class II molecules are present on many cells of the immune system, and therefore are important in modulating and mediating immune reactions. The absence of class II bearing cells in the cornea leads to the interesting issue of whether or not those antigens can induce immune rejection of a corneal graft. In the current study we have made use of a pair of congenic rat strains that differ only at class II loci to determine the impact of these antigens on corneal graft survival. Central corneal grafts were not rejected. Recipients preimmunized with skin grafts rejected 100% of the class II disparate corneas with a median survival time (MST) of 15.5 days. When class II disparate Langerhans-cell-containing (LC+) corneas were grafted, the corneas were not rejected, but they immunized the recipients as evidenced by the rejection of a second corneal graft on the contralateral eye. Immunofluorescent stains demonstrated transient expression of class II antigens on graft epithelium after transplantation. This temporary appearance of class II provides a target for rejection in the preimmunized animals but is of insufficient duration to both prime naive animals and provide a target for antigraft effectors.

Prevention of the induction of allospecific cytotoxic T lymphocyte and delayed-type hypersensitivity responses by ultraviolet irradiation of corneal allografts.

The effect of ultraviolet radiation (UVR) on the immunogenicity of corneal allografts was examined in a mouse model. Corneal allografts differing from the host at the entire MHC and multiple minor H loci were subjected to 200 mJ/cm2 of UVB irradiation immediately prior to heterotropic transplantation. Analysis of cytotoxic T lymphocyte and delayed-type hypersensitivity responses revealed that UVR treated corneal grafts failed to induce either CTL or DTH responses in C57BL/6 recipients. UVB treatment abolished the immunogenicity of highly immunogenic corneal grafts containing either resident or infiltrating donor-specific Langerhans cells. Sequential grafting experiments demonstrated that UVB-treated grafts rendered the hosts anergic to subsequent immunization with highly immunogenic corneal limbus grafts that contained dense concentrations of Ia+ Langerhans cells of donor origin. The results indicate that UV treatment not only reduces the immunogenicity of the corneal allograft but may also render it tolerogenic.

Characteristics of rejection of orthotopic corneal allografts in the rat.

We have employed a rat model of orthotopic corneal transplantation to study the characteristics of rejection and development of systemic immunity in the host. Lewis (LEW) rats underwent a true penetrating keratoplasty using Wistar-Furth (WF) donor corneas. A rejection incidence of 55% with a mean survival time (MST) of 17.1 days was observed using these untreated allogeneic corneas. Animals undergoing rejection of these allografts developed cytotoxic T lymphocytes (CTL) capable of lysing WF lymphoblasts in a standard 51-chromium release assay. These same rats did not have delayed-type hypersensitivity (DTH) responses when compared to skin grafted controls. Rats with clear allografts had no demonstrable CTL or DTH activity. As expected, LEW rats that were preimmunized with WF skin grafts and subsequently received WF orthotopic corneal grafts rejected 100% of these corneas at an accelerated rate (MST = 9.7 days, P less than .02). We then employed a previously described technique of using latex beads to induce migration of Langerhans cells into the central cornea of the donor graft prior to transplantation. The presence of Langerhans cells in the donor cornea resulted in a higher incidence of rejection (96%) and an accelerated rate (MST = 11.8 days, P less than .02) when compared to untreated allografts. These rats also had a higher level of CTL activity and marked DTH responses. These data show that rejection of orthotopic allogeneic corneas is accompanied by the development of systemic alloimmunity as measured by CTL activity. However, these fully allogeneic corneas can be rejected in the absence of DTH responses. Langerhans cells have a dramatic effect on graft survival and are necessary for induction of DTH responsiveness in the host.

Acceptance of H-Y-disparate corneal grafts despite concomitant immunization of the recipient.

Male-specific, H-Y antigen is a widely utilized antigen system for analyzing the role of non-MHC transplantation antigens in graft rejection. In this study, we examined the role of H-Y antigen in corneal graft rejection. Orthotopic corneal grafts from male LBNF1 rats were transplanted to syngeneic female LBNF1 recipients. The male corneal grafts survived beyond 100 days on naive female recipients. In other experiments, hosts bearing clear male corneal grafts and systemically immunized with subcutaneous inoculations of male splenocytes followed by full-thickness male skin grafts failed to reject their corneal grafts, even though the male skin grafts were swiftly rejected. The inability of female hosts to reject existing male corneal grafts suggested that the cornea failed to express H-Y transplantation antigen. Further experiments, however, revealed that male-specific antigen was expressed on corneal grafts. Hosts bearing clear male grafts in the left eye rejected subsequent male skin grafts and promptly rejected male corneal grafts transplanted to the contralateral eye. Interestingly, the original male corneal grafts remained clear during the rejection of both the skin graft and the second corneal graft. The results indicate that corneal grafts representing minor histocompatibility disparities enjoy immunologic privilege in the naive host, even if the host is subsequently immunized systemically.

Histopathology of rejected orthotopic corneal grafts in the rat.

We have used an orthotopic graft model in the rat to study the histologic characteristics of corneal allograft rejection. Unrejected allogeneic grafts could not be distinguished from clear syngeneic grafts. Although donor Langerhans cells are necessary for the development of delayed-type hypersensitivity (DTH), the histopathological characteristics of rejecting corneal allografts in immunologically naive hosts were identical regardless of the presence or absence of donor Langerhans cells. By contrast, preimmunization had a dramatic effect on the histology of graft rejection. Untreated allografts placed onto pre-immunized recipients underwent a marked cellular necrosis accompanied by minimal inflammation that easily distinguished these grafts from the previous groups. These results suggest that neither the presence nor absence of DTH responsiveness correlates with the histopathological events that accompany corneal graft rejection. However, preimmunization leads to a different histologic pattern of rejection that is characterized by an intense cellular necrosis.

Reactivation of inflammatory lesions in ocular histoplasmosis.

BACKGROUND: Active inflammation has not been traditionally associated with the ocular histoplasmosis syndrome. OBJECTIVE: To investigate the occurrence of presumed inflammatory chorioretinal lesions in patients with the ocular histoplasmosis syndrome. METHODS: Patients seen with acute symptoms and a clinical picture of ocular histoplasmosis were observed prospectively between August 13, 1993, and December 2, 1997. Symptoms, visual acuity, and fluorescein sodium angiography were used to document changes in inflammatory loci. RESULTS: Twelve patients were seen with active inflammatory lesions. Eleven had resolution of the loci with lessening of symptoms and improvement in acuity and angiographic findings. A typical subretinal neovascular membrane developed in 1 patient 8 months after the onset of symptoms. CONCLUSIONS: Inflammatory chorioretinal lesions can reactivate in the ocular histoplasmosis syndrome. In most of these patients, neovascularization did not develop and visual acuity was preserved.

Oral therapy in diffuse unilateral subacute neuroretinitis.

Diffuse unilateral subacute neuroretinitis is an endemic disease associated with severe visual loss in the southeastern and midwestern United States and the Caribbean. It is caused by a single nematode that may wander in the subretinal space for many months or years. Until recently, the only effective treatment has involved the difficult and time-consuming biomicroscopic detection of the worm followed by photocoagulation. This report describes the use of oral thiabendazole in four patients with presumed diffuse, unilateral, subacute neuroretinitis. Serial fundus photography was used to detect evidence of early destruction of the worm.

Choroidal neovascularization associated with choroidal nevi.

OBJECTIVE: We undertook a retrospective study of all choroidal nevi with overlying neovascularization seen at Bascom Palmer Eye Institute, Miami, Fla, to determine long-term effects on vision and whether the presence of neovascularization represented increased malignant potential of the lesion. DESIGN: A computer search of patients with a coded diagnosis of both a choroidal nevus and choroidal neovascularization was performed. Cases in which the neovascularization was directly overlying the nevus were used for the study. RESULTS: The records of 23 patients followed up for a mean of 6.5 years were reviewed for visual acuity, effect of treatment, and change in the size of the choroidal lesion. Fifteen of the 23 patients had a final visual acuity in the affected eye of 20/200 or better. Five of six patients treated with laser had visual improvement of 2 or more lines. Only one of these lesions showed any growth, and this was after 17 years of no growth. CONCLUSIONS: Choroidal neovascularization associated with choroidal nevi can have profound effects on vision. Laser treatment, when indicated, is effective and may be safely performed. The clinical course of these lesions, to date, does not indicate any clinically significant malignant transformation.

Latanoprost-associated cystoid macular edema.

PURPOSE: To report two cases in which cystoid macular edema developed after initiation of topical latanoprost for glaucoma. METHODS: Case reports. One pseudophakic eye in each of two patients treated with latanoprost for glaucoma developed decreased vision and cystoid macular edema. Latanoprost was discontinued, and the cystoid macular edema was treated with topical corticosteroids and ketorolac. RESULTS: After discontinuing latanoprost and starting corticosteroids and ketorolac, visual acuity improved from counting fingers to 20/60 in one patient's left eye and from 20/100 to 20/25 in the other patient's right eye. The macular edema resolved in both eyes. CONCLUSIONS: Topical latanoprost may be associated with cystoid macular edema; this may be related to a prostaglandin-like action.

Follow-up and ultrasonographic examination of patients with macular pseudo-operculum.

Twenty-nine patients (30 eyes) with pseudo-opercula were followed up for six to 65 months (mean, 24 months). Visual acuity was 20/30 or better in all but one eye that was amblyopic. Only one eye developed a decrease in visual acuity and changes interpreted as a stage 1 (foveal detachment induced by tangential traction of the cortical vitreous) impending hole. After vitrectomy visual acuity returned to 20/20. Ultrasonographic examination confirmed the presence of pseudo-opercula in all 22 eyes examined. We concluded that the a pseudo-operculum is a favorable prognostic sign and that its presence is demonstrable ultrasonographically.

Diagnosis of reactive lymphoid hyperplasia by chorioretinal biopsy.

We treated a patient with reactive lymphoid hyperplasia in whom the diagnosis was made by chorioretinal biopsy. Histopathologic examination and culture of the biopsied specimen allowed us to rule out a neoplastic or infectious process. The biopsy result allowed us to treat him with systemic corticosteroid alone, thus avoiding the potential harmful side effects of other medications, including antituberculous drugs. There were no surgical or postoperative complications. This study confirms the usefulness of chorioretinal biopsy for establishing a diagnosis and formulating a rational treatment plan.