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OBJECTIVE--The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of [...]

Background: The continuation of anti-vascular endothelial growth factor (anti-VEGF) treatment after achieving stability in patients with neovascular age-related macular degeneration has generally been advocated. In our own patients, we thought to assess whether continued anti-VEGF treatment is capable of preventing recurrences. Methods: In this retrospective observational case series, patients with stable disease either opted to continue treatment every 12–14 weeks (Group 1) or stopped treatment with subsequent follow-up visits every 8–12 weeks (Group 2). Results: Of the 103 eyes of 103 patients achieving stability, 49 eyes continued treatment (Group 1), whereas treatment was stopped in 54 eyes undergoing regular follow-up (Group 2). Recurrent disease was observed in 21 (42.9%) and 33 (61.1%) cases in Group 1 and Group 2, respectively (p= 0.08). Time between achieving stable disease and recurrence was comparable between Group 1 and Group 2 (11.1 ± 8.2 months vs. 9.2 ± 6.7 months; p= 0.43). The number of visits between achieving stability and disease recurrence was similar, but not the number of injections (3.5 ± 2.0 vs. 0.2 ± 0.4; p< 0.001). Conclusions: Continuing anti-VEGF therapy after achieving functional and morphological stability every 12–14 weeks does not prevent recurrences. Patients deserve to be informed of a potential lifetime risk of recurrences, even under continued therapy.

Objective: To present two different phases of progression of Gass stage 1 foveolar detachment to lamellar or full-thickness macular holes revealed with spectral domain optical coherence tomography.Design: This is an observational study.Participants: The medical records of four patients (four eyes) with foveolar detachment that had evolved into stage 1 macular holes were compared. The patients manifested neither co-existing myopia nor any other ocular pathology.Methods: At each consultation, best-corrected visual acuity, dilated fundus examination, and spectral domain optical coherence tomography were performed to ascertain whether the foveolar detachment was associated with posterior vitreal detachment.Results: In two of the eyes, and at an early phase of the disease, an incomplete posterior vitreal detachment and vitreal adhesion at the head of the optic nerve were observed. In the other two cases, the traction was not antero-posterior but tangential and had been effected by thickening of the inner limiting membrane or by the presence of a discrete epiretinal membrane in the papillomacular area; the posterior vitreal detachment was complete. In the former two cases and in one of the latter, the foveolar detachments had progressed to full-thickness macular holes. The visual acuities were better in the latter than in the former two eyes.Conclusion: Two different pathological mechanisms appear to underlie the formation of macular holes: The optical coherence tomography–guided classification of Gass stage 1 macular hole as an antero-posterior traction with a triangular foveolar detachment has to be distinguished from a tangential traction and a complete posterior vitreal detachment. Tangential traction is typically associated with a more dome-shaped or irregular foveolar detachment and a hyper-reflective band at the vitreoretinal interface.

To examine vision-related quality of life in patients with diabetic macular edema (DME) treated with intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY).

To report outcomes in patients with neovascular age-related macular degeneration (nAMD) after treatment with aflibercept for up to 4 years using a treat-and-extend (T&E) regimen.

In many case series, anatomical but not functional improvements have been documented after a switch in therapy from ranibizumab to aflibercept. We wished to compare the outcomes of eyes that had undergone a switch in therapy from ranibizumab to aflibercept because of a high treatment demand or for other reasons.

BACKGROUND AND OBJECTIVES:The aim of this study was to identify the rate of early visual acuity poor responders in patients with neovascular age-related macular degeneration (AMD) after the first intravitreal injection of ranibizumab (Lucentis; Genentech, South San Francisco, CA) and to determine potential predictors for early response.PATIENTS AND METHODS:Patients with choroidal neovascularization secondary to AMD were evaluated before and 1 month after their first ranibizumab treatment. Early poor responders were defined as eyes gaining less than five letters 1 month after the first injection.RESULTS:Following the first ranibizumab injection, 58% of 84 patients gained five or more letters. Beyond 42% poor responders, 31% displayed foveal retinal pigment epithelium (RPE) atrophy and 89% a loss of the external limiting membrane (ELM) integrity at baseline. However, the amount of intra- and subretinal fluid, pigment epithelial detachment (PED), and subfoveal fibrosis showed a similar distribution between gainers and poor responders.CONCLUSION:Early poor responders present with more RPE atrophy, as well as a loss of the ELM integrity at baseline optical coherence tomography.[[Ophthalmic Surg Lasers Imaging Retina.2017;48:326–332.]

Long-term evolution of congenital toxoplasmosis is not documented. We assessed the outcome of treated congenital toxoplasmosis in a cohort of adult individuals who had undergone ante- and postnatal treatment to provide information for pediatricians and parents on the evolution of the disease.

Purpose: To present a rare case of bilateral conjunctival molluscum contagiosum (MC) in an HIV-positive individual who had unilateral lesion excision before induction of highly active antiretroviral therapy (HAART), and to discuss the pathophysiological consequences of immune restoration. Methods: Case report: A 40-year-old male Caucasian presented with atypical, bilateral lesions of the limbal conjunctiva due to MC. Before the induction of HAART, nodules in the left eye were excised whilst the single lesion in the right eye was left untouched. Results: The clinical diagnosis of conjunctival MC was confirmed histopathologically. Six months after the induction of HAART, the untouched lesion (right eye) had regressed and there was pronounced local injection of the conjunctiva. MC lesions did not recur after excision (left eye), and signs of inflammation were absent. Conclusion: Conjunctival MC is rare and associated with immune deficiency. To the best of our knowledge, the presented case is the first reported instance of bilateral, multi-lesional MC of the conjunctiva in an HIV-positive patient undergoing HAART. Attention must be paid to the possible complications associated with the restoration of immunocompetence.

ABSTRACTThe purpose of this study was to compare the local and systemic Toxoplasma-specific humoral immune responses in individuals with ocular toxoplasmosis (OT). To this end, paired aqueous humor and serum samples from 46 individuals with active OT and from 30 individuals without inflammatory eye disease (controls) were analyzed by immunoblotting for anti-Toxoplasmaimmunoglobulin G (IgG), IgA, IgM, and IgE directed against 20- to 120-kDa antigens. The presence in the aqueous humor of a unique band, or of at least three bands that were at least three times more intense in aqueous humor than in serum, was taken as evidence of local antibody production. IgG bands were detected in 98% of the aqueous humor samples, while IgA bands were detected in 76%, IgM bands were detected in 8%, and IgE bands were not detected in any. Evidence of local production of specific antibodies was found in 32 cases (70%) (IgG in 23 [50%]; IgA in 16 [35%]). In 10 instances (22%), routine laboratory tests were not indicative of OT. In 14 cases (30%), no local antibody production was detected by immunoblotting; 3 of these cases yielded evidence of local antibody production according to the Goldmann-Witmer coefficient. Local antibody production was revealed for 7 of the 30 controls (23%). Hence, the sensitivity of immunoblotting for IgG and IgA is 70%, and the specificity is 77%. We conclude that immunoblotting for local specific IgG and IgA supports the clinical diagnosis of OT in 70% of cases. In 22% of these, the diagnosis is not confirmed by other laboratory tests. Hence, immunoblotting increases the sensitivity of routine laboratory tests and should be considered for samples that register negative by such tests.

Purpose To report an unusual case of almost simultaneous bilateral rhegmatogenous retinal detachment in the context of external-beam radiotherapy for a tumor at a non-ocular target site and in the absence of pre-existing ocular pathology. Methods Observational case report with review of corresponding literature. Results A 63-year-old man was referred for bilateral retinal detachment which was associated with many horseshoe tears and proliferative vitreoretinopathy. He had undergone surgery for a carcinoma of the left maxillary sinus 4 months prior to the presentation and had then received external-beam radiotherapy for 3 months. There was no familial history of retinal detachment and/or eye trauma in this hyperopic patient with clear native lenses. No chorioretinal pathology was apparent that could have predisposed the retinas to tearing. Conclusions Simultaneous bilateral retinal detachment is exceptional, especially in a patient with no risk factors. The effect of radiotherapy on the vitreoretinal interface is discussed in the light of existing data and may have been responsible for our patient’s retinal detachment.

The combined influence of congenital toxoplasmosis and twin pregnancy on the duration of gestation has not been previously examined. Similarly little is known about the influence of genetic factors on the clinical course of this disease. The present study addresses these issues.

Neurospecific acetylcholinesterase inhibitors have been shown to lower intraocular pressure (IOP) in normal rabbits and might have additional neuroprotective effects. This study was set out to explore and compare the toxicity of two selective acetylcholinesterase inhibitors, rivastigmine and donepezil, on two standardized cell lines of epithelial origin. Chang and Vero cells were incubated with various concentrations of rivastigmine or donepezil. Acute toxicity (4 h) was assessed by monitoring the permeability of cells to propidium iodide. Chronic toxicity (7 days) was determined by monitoring the effect of the two drugs on esterase activity and cell proliferation. The viability of cells was also assessed morphologically by microscopic inspection. Signs of acute toxicity became manifest at a rivastigmine concentration of 50 mg/ml in both Chang and Vero cells. Indications of chronic toxicity became obvious at concentrations of as low as 1 × 10–5 mg/ml. In contrast, degenerative morphological changes became manifest only at a concentration of as high as 1 mg/ml. In donepezil-treated cells, acute toxicity was not observed in the concentration range tested, whereas chronic toxicity was detected at 1 × 10–1 mg/ml in both Chang and Vero cells, a concentration at which degenerative morphological changes became evident as well. In contrast to rivastigmine, donepezil elicited no signs of acute or chronic toxicity in either Chang or Vero cells at the IOP-lowering concentration of 1 × 10–4 mg/ml. At this dose, the drug is therefore unlikely to evoke deleterious effects on ocular surface tissues in the clinical setting.

Augenverletzungen sind heute der häufigste Grund einer einseitigen Erblindung. Fortschritte sind in den letzten 15 Jahren sowohl in der Diagnostik (CT, MRI, Ultraschall) als auch in der chirurgischen Behandlung von extra- und intraokularen Verletzungen erzielt worden. Zu erwähnen sind die Pars-plana-Vitrektomie, intraokulare Langzeittamponaden bei instabiler Netzhautsituaton, verfeinerte Techniken der Phakoemulsifikation, verbesserte Intraokularlinsen und sulkus-fixierte Intraokularlinsen. Zudem wurde in den letzten Jahren das Spektrum der Möglichkeiten einer adjuvanten Pharmako-Therapie zur Behandlung von Augenunfällen erheblich erweitert. Anhand zahlreicher Beispiele (Erosio, Verätzung, Hyphäma, Katarakt, photothermische Netzhautläsion und Optikusneuropathie) sollen die aktuellen Möglichkeiten der medikamentösen Therapie traumatischer Augenveränderungen vorgestellt werden.

Die herpetische Keratitis und Uveitis sind vermutlich die häufigst verkannten Erkrankungen der vorderen Augenabschnitte, obwohl sie die wichtigste entzündliche Erblindungsursache in unseren Breitengraden darstellen. Der rezidivierende Verlauf ist typisch, fast pathognomonisch für die herpetische Augenaffektion und verantwortlich für deren hohen Krankheitskosten. In der letzten Zeit wurden auf der Basis modernster molekularbiologischer Diagnostik und langjähriger multizentrischer klinischer Studien wichtige Erkenntnisse gewonnen, die die Grundlage für unser pathophysiologisches Verständnis der Erkrankung und die Basis moderner Behandlungskonzepte darstellen. In dem vorliegenden Artikel werden nach einer allgemeinen pathophysiologischen Einführung in das Thema auf diesem Hintergrund die einzelnen Krankeitsbilder (epitheliale und geographische Keratitis, stromale Keratitis, disziforme Keratitis/Endothelitis, Uveitis und metaherpetische Keratitis) vorgestellt und aktuelle Strategien zu Behandlung und Rezidivprophylaxe erörtert. Es werden Überlegungen zur Entstehung von Rezidiven angestellt und schließlich kurz auf die sozialmedizinische Bedeutung der Erkrankung eingegangen. Zusammen mit den klinischen Abbildungen sollen die Informationen dem praktisch tätigen Arzt die Einschätzung der regelmäßig im Zusammenhang damit auftauchenden Probleme erleichtern und die therapeutischen Möglichkeiten und Grenzen aufzeigen.

Die Behandlung der HIV-Infektion und ihrer Folgen stellt wegen der teils massiven Nebenwirkungen der Therapie heute ein erhebliches Problem dar. Inakzeptable Nebenwirkungen der Therapie erzwingen nicht selten eine suboptimale antiretrovirale Therapie bis hin zum Therapie-Abbruch. Damit stehen die HIV-assoziierten Sekundärprobleme auch heute noch im Zentrum der Betreuung betroffener Patienten. Im Bereich der Augen gibt es heute drei Erkrankungen, die man bei diesen Patienten regelmäßig antrifft: Die HIV-assoziierte retinale Mikroangiopathie, die CMV-Retinitis und die Immunrekonvaleszenz-Uveitis. Die retinale Mikroangiopathie erlangt Bedeutung, weil sie Ausdruck einer nicht kontrollierten Virusreplikation ist. Die virale Retinitis zeigt den aktuellen Verlust der funktionellen Immunkontrolle und wird heute auch bei CD4-Zelldichten oberhalb 100 Zellen pro Mikroliter gesehen. Die Therapie dieser Erkrankung wird zunehmend kritisch, da die Patienten wesentlich länger überleben und nicht abzuschätzen ist, für wie lange eine systemische Rezidivprophylaxe erforderlich ist. Die eventuelle Erholung des Immunsystems sorgt aber auch für Probleme, insbesondere die Immunrekonvaleszenz-Uveitis. Diese ist nicht immer einfach von einer Reaktivierung der viralen Retinitis abzugrenzen und kann auch zu langfristigen Sehstörungen führen.

ABSTRACTTo evaluate the diagnostic sensitivity of a panel of laboratory tests for ocular toxoplasmosis performed at the time of presentation, paired samples of aqueous humor and serum were collected from 49 consecutive episodes of ocular toxoplasmosis with a clinical course of less than 3 weeks. Total immunoglobulin G (IgG) andToxoplasma gondii-specific IgG, IgM, and IgA were quantified by enzyme-linked immunosorbent assay. The avidity ofT. gondii-specific IgG was determined, and DNA extracted from aqueous humor was amplified for detection of a glycoprotein B gene sequence of T. gondii. The diagnosis was confirmed for 73% (36 of 49) of the patients; this rate rose to 79.5% if data from a later analysis of aqueous humor derived from five of the negative patients were included. The analysis of serum (detection of T. gondii-specific IgM and analysis of consecutive serum samples) alone did not contribute to the diagnosis. Calculation of local antibody production lacked diagnostic sensitivity when it was determined less than 3 weeks after the manifestation of clinical symptoms (28 of 49 patients [57%]), but this rose to 70% after an analysis of a second aqueous humor sample. The antibody avidity index attained diagnostic significance in only 8 of 43 instances (19%), andT. gondiiDNA was amplified from no more than 6 of 39 (16%) aqueous humor samples. However, T. gondii-specific IgA was found within the aqueous humors of 11 of 43 patients (26%); measurement of the T. gondii-specific IgA level thus contributed substantially to the diagnostic sensitivity of the laboratory tests.

AbstractPurpose:Investigations of the course of ocular toxoplasmosis and the influence of a host’s immunological status in an animal model would contribute to our understanding of the pathophysiology underlying this condition. In the current study, these aspects are addressed using naive and primed rabbits infected transvitreally with the non-cyst-forming BK strain of Toxoplasma gondii.Materials and Methods:Of 45 latex agglutination test-negative rabbits, 27 were infected subcutaneously with 5,000 Toxoplasmatachyzoites, and the ensuing infection treated by systemic administration of clindamycin for 20 days. Four of these rabbits died from generalized infection. The remaining 23 primed rabbits were then inoculated periretinally with a further 5,000 Toxoplasmatachyzoites, administered via the transvitreal route; the 18 naive rabbits were treated likewise. Results:All 18 naive and 21 of the 23 primed rabbits developed toxoplasmic retinochoroiditis. As regarded progression of the disease, dissemination of the condition (p = 0.0001), degree of vitreal infiltration (p = 0.0001) and incidence of retinal detachment (p < 0.05) were all more pronounced in the naive group. Despite treatment, 4 of the 18 (22%) naive rabbits died from generalized infection, as did 4 of the 27 (15%) subcutaneously infected ones (prior to periretinal infection). In the primed (secondarily infected) animal group, only moderate signs of systemic infection were manifested, and there were no fatalities. Conclusion:The high incidence (> 90%) of retinochoroiditis achieved even in primed animals, by introducing Toxoplasmatachyzoites via the transvitreal route, may reflect the maintenance of an intact uveovascular barrier during the early stages of the disease. The pattern of infection, in being restricted primarily to the retina, mimics the situation evinced in humans. Regarding propagation of the disease, the condition manifested in naive rabbits resembles that occurring in immunodeficient patients, whereas that evoked in primed animals corresponds to recurrence of infection in immunocompetent patients.

Fluid samples derived from 451 organ cultured corneae were tested for the presence of HSV‐1 DNA after electroseparation and amplification for fragments of the glycoprotein D‐ and thymidine kinase‐encoding genes. Of the culture media, 134 were processed immediately after withdrawal (Group 1); 100 were stored at ambient temperature for 6 to 60 weeks (Group 2); 90 were stored at −8°C for 4 to 9 weeks (Group 3); and 127 were stored at −20°C for 2 to 30 weeks (Group 4). The degradation of human DNA (marker gene, betaglobin) under these different storage conditions and of human and HSV‐1 DNA as a sequential function of time at ambient temperature was gauged by the loss of a detectable signal for the respective component. Endothelial cell density within each of the corneal discs was determined before and after organ culture.

In immunocompetent individuals, necrotizing retinopathy is a rare complication of chickenpox. Herein, we report on a 3-year-old immunocompetent boy who developed retinitis and optic neuritis 3 days after the onset of chickenpox and compare the findings to published cases. Since macula and optic nerve were affected, visual acuity remained poor. An early diagnosis and treatment of ocular manifestations in chickenpox is imperative for the preservation of a residual visual function and prevention of blinding secondary complications.

Background: Dosing recommendations for the treatment of pregnancy-acquired toxoplasmosis are empirical and widely based on experimental data. There are no pharmacological data on pregnant women with acute Toxoplasma gondiiinfection under treatment with pyrimethamine (PY) and sulfadiazine (SA) and our study intends to tighten this gap. Methods: In this retrospective case–control study, we included 89 pregnant women with primary Toxoplasmainfection (PT) treated with PY (50 mg first dose, then 25 mg/day), SA (50 mg/kg of body weight/day), and folinic acid (10–15 mg per week). These were compared to a group of 17 women with acute ocular toxoplasmosis (OT) treated with an initial PY dose of 75 mg, thereafter 25 mg twice a day but on the same SA and folinic acid regimen. The exact interval between drug intake and blood sampling and co-medication had not been recorded. Plasma levels of PY and SA were determined 14 ± 4 days after treatment initiation using liquid chromatography–mass spectrometry and compared using the Mann–Whitney Utest at a p&lt; 0.05 level. Results: In 23 PT patients (26%), SA levels were below 20 mg/l. Fifteen of these 23 patients (17% of all patients) in parallel presented with PY levels below 700 µg/l. Both drug concentrations differed remarkably between individuals and groups (PY: PT median 810 µg/l, 95% CI for the median [745; 917] vs. OT 1230 µg/l [780; 1890], p= 0.006; SA: PT 46.2 mg/l [39.9; 54.4] vs. OT 70.4 mg/l [52.4; 89], p= 0.015) despite an identical SA dosing scheme. Conclusions: SA plasma concentrations were found in the median 34% lower in pregnant women with PT compared to OT patients and fell below a lower reference value of 50 mg/l in a substantial portion of PT patients. The interindividual variability of plasma concentrations in combination with systematically lower drug levels and possibly a lower compliance in pregnant women may thus account for a still not yet supportable transmission risk. Systematic drug-level testing in PT under PY/SA treatment deserves to be considered.

Abstract

We report the vertical transmission of congenital toxoplasmosis from a chronically infected immunocompetent woman to her child. On the background of published knowledge in this field, vertical transmission must have developed after maternal reinfection or reactivation of the preexisting disease.