Dupilumab-Induced, Tralokinumab-Induced, and Belantamab Mafodotin-Induced Adverse Ocular Events-Incidence, Etiology, and Management.

ABSTRACT: Emerging monoclonal antibody therapies are assuming greater importance in the management of severe and refractory forms of immunity-driven and oncological disorders. However, some have been found to induce adverse ocular events (AOEs) leading to discontinuation of treatment or additional multidisciplinary management. We present the current knowledge concerning AOEs associated with 3 monoclonal antibody therapies: dupilumab, tralokinumab, and belantamab mafodotin. We examine the manifestations of their AOEs, proposed pathophysiological mechanisms, and current treatment recommendations. We identified and reviewed all studies for dupilumab, tralokinumab, and belantamab mafodotin using the keywords "dupilumab," "tralokinumab," "belantamab mafodotin," "conjunctivitis," and "keratopathy" from January 2016 to November 2021. Conjunctivitis was the most frequently reported AOE in patients with atopic dermatitis receiving dupilumab or tralokinumab. Mild cases were managed with warm compresses for associated meibomian gland dysfunction, artificial tears, and antihistamine/mast cell stabilizer eye drops. In more severe cases, additional anti-inflammatory therapy, with corticosteroid eye drops or ointments, or topical calcineurin inhibitors-such as tacrolimus or ciclosporin-were required. Patients with resistant or refractory multiple myeloma treated with belantamab mafodotin often developed keratopathy, which could necessitate contact lens fitting, or for cycles of belantamab mafodotin to be delayed.

Initial Clinical Results With a Novel Monofocal-Type Intraocular Lens for Extended Macular Vision in Patients With Macular Degeneration.

PURPOSE: To determine the feasibility of a novel intraocular lens (IOL) designed to improve retinal image quality at up to 10° of retinal eccentricity and optionally provide retinal magnification in patients with macular disease. METHODS: In this prospective, interventional pilot study, 8 eyes of 7 patients with bilateral dry age-related macular degeneration and 1+ or less cataract underwent phacoemulsification and capsular bag implantation of a single, injectable, hydrophobic acrylic IOL. Safety and efficacy were assessed by monitoring logMAR corrected distance and near visual acuity, intraocular pressure, specular microscopy, 80-point visual field testing, and anterior segment and macular optical coherence tomography at baseline and 1 week, 1 month, and 2 months postoperatively. Microperimetry was undertaken at baseline and 1 and/or 2 months postoperatively. Reading performance was assessed at baseline and 1 month postoperatively using the Minnesota low vision reading chart (MNREAD; Precision Vision, LaSalle, IL). RESULTS: Safety outcomes were equivalent to standard monofocal IOLs. Visual acuities improved in all patients. Mean corrected distance visual acuity improved from 0.93 ± 0.22 preoperatively to 0.59 ± 0.25 at 2 months postoperatively. Mean reading speed increased from 28 ± 19 to 44 ± 31 words per minute. Mean microperimetry threshold sensitivities increased from 8.2 ± 4.6 to 12 ± 5.6 dB. Mean percentage of fixation points within a 4° circle increased from 77% ± 17% to 91% ± 11% with evidence for progressive movement of preferred retinal loci away from areas of geographic atrophy. CONCLUSIONS: Initial results indicate this novel IOL has a safety profile comparable with standard IOLs. Visual benefits may exceed those obtained with existing technologies in patients with macular disease. Further work is required to determine the full potential of extended macular vision technology. [J Refract Surg. 2018;34(11):718-725.].

Influence of Socioeconomic Deprivation on Visual Acuity in Patients Undergoing Corneal Transplantation.

PURPOSE: To determine whether there is an association between socioeconomic status and best-corrected visual acuity (BCVA) in patients undergoing corneal transplantation in the United Kingdom. METHODS: Retrospective cohort study of 4306 patients registered on the national United Kingdom Transplant Registry and undergoing penetrating keratoplasty, anterior lamellar keratoplasty, or endothelial keratoplasty in 2002, 2008, and 2013. Socioeconomic status was determined by applying a validated deprivation index to generate a score based on 5 categories. Patients' demographic details, preoperative BCVA, copathology, surgical center volume, and socioeconomic status were analyzed for univariate effects of categorical and continuous variables. Binary logistic regression was used to determine whether preoperative BCVA was affected by socioeconomic status after adjusting for other factors. RESULTS: A larger percentage of the most deprived group was female in each period compared with the least deprived, but this was only significant in 2002 (48.7% vs. 40.3%; P = 0.04). There was no interaction between socioeconomic status and the preoperative BCVA in the grafted eye. However, BCVA in the fellow eye was poorer for the most economically deprived patients compared with the least deprived in 2013 (P = 0.01). CONCLUSIONS: We found no evidence of a relationship between socioeconomic deprivation and BCVA in the transplant recipient eye. However, there was clear evidence of an association between socioeconomic deprivation and reduced acuity in fellow eyes, for which barriers to access or low patient demand may be possible contributors.

Consecutive case series of 244 age-related macular degeneration patients undergoing implantation with an extended macular vision IOL.

PURPOSE: To determine safety and visual outcomes in eyes with age-related macular degeneration (AMD) implanted with a novel intraocular lens (IOL) that delivers an optimized retinal image to all macular areas within 10 degrees of retinal eccentricity. METHODS: This was a consecutive case series of 244 eyes with dry/stable wet AMD and logMAR visual acuity ≥0.3 implanted with iolAMD Eyemax monoTM (London Eye Hospital Pharma), a single-piece, injectable, hydrophobic acrylic IOL sited in the capsular bag. Primary outcome was safety. Secondary outcomes were changes in corrected distance visual acuity (CDVA) and corrected near visual acuity (CNVA) (logMAR). RESULTS: Mean age at surgery was 80 years. Mean duration of follow-up was 3 months (range 1-16 months). No eyes had worsening of CDVA. Frequency of perioperative complications was equivalent to standard IOL implantation. Postoperative refractive outcomes were within ±1 D of the target refraction in 88% of cases. Mean preoperative CDVA improved from 1.06 to 0.71 postoperatively (mean of differences -0.35; 95% confidence interval [CI] -0.3886 to -0.3223; p<0.0001), equating to an approximate Early Treatment Diabetic Retinopathy Study gain of 18 letters. Mean preoperative CNVA (N-point; logMAR conversion) improved from 1.36 to 0.88 postoperatively (mean of differences -0.48; 95% CI -0.53 to -0.44; p<0.0001). CONCLUSIONS: This novel IOL appears safe in the short to medium term. Improvements in postoperative CDVA and CNVA exceed those observed with standard implants.

First Results of a New Hyperaspheric Add-on Intraocular Lens Approach Implanted in Pseudophakic Patients with Age-Related Macular Degeneration.

PURPOSE: To determine the visual outcomes of the EyeMax Mono intraocular lens (IOL) technology (London Eye Hospital Pharma, London, UK), which is a foldable and injectable hydrophobic acrylic IOL implanted as an add-on solution in pseudophakic eyes with age-related macular degeneration, in a pilot study. DESIGN: A prospective, interventional case series. PARTICIPANTS: A total of 22 pseudophakic eyes (11 patients) with bilateral severe or intermediate dry age-related macular degeneration (AMD) (13 eyes) or stable wet AMD or disciform scarring (9 eyes) meeting the criteria for sulcal IOL implantation. METHODS: Both eyes of participating subjects underwent small-incision ciliary sulcal implantation of a hyperaspheric, soft hydrophobic acrylic intraocular lens designed to improve the quality of the retinal image in all areas of the macula ≤10° from fixation and to generate a moderate hypermetropic correction for magnification. MAIN OUTCOME MEASURES: The primary outcome was safety as determined by intra- and postoperative complications, raised intraocular pressure requiring medical or surgical intervention, postoperative diplopia, reduction in visual field, and loss of ≥2 lines of visual acuity. Secondary outcomes were improvements in subjective and objective visual acuity (logarithm of the minimum angle of resolution). RESULTS: No intraoperative complication occurred. Elevated intraocular pressure values were measured directly after the operative procedure in 2 eyes (25 mmHg and 27 mmHg) and at the 1-week postoperative visit in 1 eye (22 mmHg) but not later. The mean postoperative spherical equivalent of refraction changed to +2.5 diopters, and all eyes had gained ≥2 lines of visual improvement (corrected distance visual acuity) by 6 months after surgery. Corrected near visual acuity as well as corrected distance visual acuity improved over time, suggesting a neuroadaptive component to improved visual function with the device. Devices were implanted bilaterally in all patients, and there were no reported symptoms of dysphotopsia or diplopia. CONCLUSIONS: Safety concerns were not identified in the short-term or medium term. These results indicate the potential of the EyeMax Mono IOL to improve near and distance visual acuity in pseudophakic eyes with intermediate to severe AMD.

Enhanced Ccl2-Ccr2 signaling drives more severe choroidal neovascularization with aging.

The impact of many inflammatory diseases is influenced by age-related changes in the activation of resident and circulating myeloid cells. In the eye, a major sight-threatening consequence of age-related macular degeneration is the development of severe choroidal neovascularization (CNV). To identify the molecular pathways and myeloid cell populations involved in this increased neovascular response, we characterized the immune status of murine choroid and retina during aging and in the context of experimental CNV. In the choroid, but not in the retina, advancing age is associated with proinflammatory upregulation of CCL2-CCR2 signaling. Genetic excision of CCL2 diminishes age-related inflammatory changes in the choroid, with reduced recruitment of proinflammatory myeloid cells and attenuation of CNV. These findings indicate that CCL2-driven recruitment of myeloid cells contributes to increased severity of CNV with age. Similar mechanisms may be involved in other age-related inflammatory diseases.

Injectable intraocular telescope: Pilot study.

PURPOSE: To assess the feasibility of a new injectable telescopic intraocular lens (IOL). SETTING: London Eye Hospital, London, United Kingdom. DESIGN: Prospective interventional pilot study. METHOD: Eyes with bilateral, intermediate, or advanced dry age-related macular degeneration (AMD); preoperative decimal corrected distance visual acuity (CDVA) of 0.25 or less; and improvement with extraocular simulation of the intervention had implantation of 2 IOLs designed for use together in a Galilean telescope configuration (iolAMD). Patients were followed for 4 months. Safety was assessed by monitoring visual acuity, intraocular pressure, specular microscopy, and anterior segment and macular optical coherence tomographies. Fixation stability and macular sensitivity were determined using microperimetry in some eyes. RESULTS: There were no significant intraoperative or postoperative complications. In 1 eye, an anterior sulcus IOL was replaced; there were no sequelae. The mean endothelial cell density was reduced by 18%. The mean decimal CDVA improved from 0.12 preoperatively to 0.20 at 4 months, a 67% gain. The mean change in spherical equivalent after implantation was -1.5 diopters (D) with 0.5 D of induced astigmatism. Microperimetric testing indicated a magnification effect and a deviation of the retinal image by up to 5 degrees, with improved fixation stability. CONCLUSIONS: This injectable intraocular miniature telescope appears safe in the short to medium term and capable of improving visual function. No significant issues were encountered regarding candidate eye selection or patient retention and cooperation. Further work is needed to evaluate the safety and efficacy of the device, particularly with respect to daily-living activities and the range of indications. FINANCIAL DISCLOSURE: Dr. Qureshi has a financial interest in London Eye Hospital Pharma. No other author has a financial or proprietary interest in any material or method mentioned.

Spectral sensitivity measurements reveal partial success in restoring missing rod function with gene therapy.

Restored rod visual function after gene therapy can be established unequivocally by demonstrating that, after dark adaptation, spectral sensitivity has the shape characteristic of rods and that this shape collapses to a cone-like shape before rods have recovered after an intense bleach. We used these tests to assess retinal function in eight young adults and children with early-onset severe retinal dystrophy from Phase II of a clinical gene-therapy trial for RPE65 deficiency that involved the subretinal delivery of a recombinant adeno-associated viral vector carrying RPE65. We found substantial improvements in rod sensitivity in two participants: dark-adapted spectral sensitivity was rod-like after treatment and was cone-like before rods had recovered after a bleach. After 40 min of dark adaptation, one participant showed up to 1,000-fold sensitivity improvements 4 months after treatment and the second up to 100-fold improvements 6 months after treatment. The dark-adapted spectral sensitivities of the other six participants remained cone-like and showed little improvement in sensitivity.

Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability.

Choroidal neovascularization (CNV) is a defining feature of wet age-related macular degeneration. We examined the functional role of CCR3 in the development of CNV in mice and primates. CCR3 was associated with spontaneous CNV lesions in the newly described JR5558 mice, whereas CCR3 ligands localized to CNV-associated macrophages and the retinal pigment epithelium/choroid complex. Intravitreal injection of neutralizing antibodies against vascular endothelial growth factor receptor 2, CCR3, CC chemokine ligand 11/eotaxin-1, and CC chemokine ligand 24/eotaxin-2 all reduced CNV area and lesion number in these mice. Systemic administration of the CCR3 antagonists GW766994X and GW782415X reduced spontaneous CNV in JR5558 mice and laser-induced CNV in mouse and primate models in a dose-dependent fashion. Combination treatment with antivascular endothelial growth factor receptor 2 antibody and GW766994X yielded additive reductions in CNV area and hyperpermeability in mice. Interestingly, topical GW766994X and intravitreal anti-CCR3 antibody yielded strong systemic effects, reducing CNV in the untreated, contralateral eye. Contrarily, ocular administration of GW782415X in primates failed to substantially elevate plasma drug levels or to reduce the development of grade IV CNV lesions. These findings suggest that CCR3 signaling may be an attractive therapeutic target for CNV, utilizing a pathway that is at least partly distinct from that of vascular endothelial growth factor receptor. The findings also demonstrate that systemic exposure to CCR3 antagonists may be crucial for CNV-targeted activity.

IL-4 regulates specific Arg-1(+) macrophage sFlt-1-mediated inhibition of angiogenesis.

One of the main drivers for neovascularization in age-related macular degeneration is activation of innate immunity in the presence of macrophages. Here, we demonstrate that T helper cell type 2 cytokines and, in particular, IL-4 condition human and murine monocyte phenotype toward Arg-1(+), and their subsequent behavior limits angiogenesis by increasing soluble fms-like tyrosine kinase 1 (sFlt-1) gene expression. We document that T helper cell type 2 cytokine-conditioned murine macrophages neutralize vascular endothelial growth factor-mediated endothelial cell proliferation (human umbilical vein endothelial cell and choroidal vasculature) in a sFlt-1-dependent manner. We demonstrate that in vivo intravitreal administration of IL-4 attenuates laser-induced choroidal neovascularization (L-CNV) due to specific IL-4 conditioning of macrophages. IL-4 induces the expression of sFlt-1 by resident CD11b(+) retinal microglia and infiltrating myeloid cells but not from retinal pigment epithelium. IL-4-induced suppression of L-CNV is not prevented when sFlt-1 expression is attenuated in retinal pigment epithelium. IL-4-mediated suppression of L-CNV was abrogated in IL-4R-deficient mice and in bone marrow chimeras reconstituted with myeloid cells that had undergone lentiviral-mediated shRNA silencing of sFlt-1, demonstrating the critical role of this cell population. Together, these data establish how lL-4 directly drives macrophage sFlt-1 production expressing an Arg-1(+) phenotype and support the therapeutic potential of targeted IL-4 conditioning within the tissue to regulate disease conditions such as neovascular age-related macular degeneration.

Long-term effect of gene therapy on Leber's congenital amaurosis.

BACKGROUND: Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. METHODS: We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. RESULTS: Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. CONCLUSIONS: Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).

An aspheric intraocular telescope for age-related macular degeneration patients.

We have designed an intraocular telescope for the posterior chamber of the human eye of patients with age related macular degeneration. The basic design is composed of two decentered high optical power lenses ( + 66D and -66D) inducing a 3° prismatic effect to project a magnified central field of view into a healthier location off the central fovea. Aspheric surfaces were used to ensure a compromise between good optical quality and high tolerance to the final axial position of both lenses after surgery. With this particular design, the telescope affords an extended range of depth of focus, high tolerance to different axial lengths of the eye and robustness against typical values of astigmatism and higher order aberrations. The final design has been manufactured in a foldable material and is compact enough to facilitate surgical implantation. This telescope is a simple but promising intraocular visual aid for AMD patients.

Nature of the visual loss in observers with Leber's congenital amaurosis caused by specific mutations in RPE65.

PURPOSE: To characterize visual losses associated with genetic mutations in the RPE65 gene that cause defects in the RPE-specific isomerase, RPE65. RPE65 is an important component of the retinoid cycle that restores 11-cis-retinal after its photoisomerization to its all-trans form. The defects investigated here cause Leber's congenital amaurosis (LCA2), an autosomal, recessively-inherited, severe, congenital-onset rod-cone dystrophy. METHODS: Vision was assessed in nine patients and 10 normal controls by measuring: (1) long-wavelength sensitive (L-) cone temporal acuity (critical flicker fusion frequency or cff) as a function of target illuminance, and (2) L-cone temporal contrast sensitivity as a function of temporal frequency at a fixed-target illuminance. Measurements were made by modulating either a 650-nm light superimposed on a 480-nm background or the red phosphor of a color monitor on a background produced by the monitor's blue phosphor. RESULTS: RPE65-mutant observers have severely reduced cffs with shallower cff versus log illuminance functions that rise with a mean slope of 4.53 Hz per decade of illuminance compared with 8.69 Hz in normal controls. Consistent with the cff differences, RPE65-mutant observers show losses in temporal contrast sensitivity that increase rapidly with temporal frequency. CONCLUSIONS: All RPE65-mutant observers have consistent and substantial losses in temporal acuity and sensitivity compared with normal observers. The losses can be characterized by the addition of two sluggish filters within the mutant visual pathway, both filters with a time constant of 29.5 ms (i.e., low-pass filters with cut-off frequencies of 5.40 Hz).

The relevance of chemokine signalling in modulating inherited and age-related retinal degenerations.

Systemic monocytes, tissue resident macrophages, dendritic cells and microglia have specific roles in immune surveillance and maintenance of tissue homeostasis and are key regulator and effector cells of the local immune response to acute and chronic tissue injury.Two major signalling pathways that differentially define trafficking behaviour and activation of systemic and local myeloid cell populations in response to exogenous and endogenous inflammatory stimuli are the Ccl2-Ccr2 and the Cx3cl1-Cx3cr1 chemokine pathways.Alterations in these pathways have been implicated in controlling myeloid cell activation during normal ageing and in age-related retinal degenerations, including age-related macular degeneration (AMD).We review the evidence for how altered chemokine signalling in acute and chronic inflammatory conditions regulate local and systemic myeloid cell responses in the retina and how this may contribute to or attenuate pathology in inherited and age-related retinal diseases. We discuss the role of environmental factors (e.g. light exposure) and the influence of genetic factors on the manifestation of pathology in experimental models and in human patients and how we envisage harnessing this knowledge for the development of targeted, more broadly applicable anti-inflammatory treatment strategies for a wide range of retinal degenerations.

CD200R signaling inhibits pro-angiogenic gene expression by macrophages and suppresses choroidal neovascularization.

Macrophages are rapidly conditioned by cognate and soluble signals to acquire phenotypes that deliver specific functions during inflammation, wound healing and angiogenesis. Whether inhibitory CD200R signaling regulates pro-angiogenic macrophage phenotypes with the potential to suppress ocular neovascularization is unknown. CD200R-deficient bone marrow derived macrophages (BMMΦ) were used to demonstrate that macrophages lacking this inhibitory receptor exhibit enhanced levels of Vegfa, Arg-1 and Il-1ß when stimulated with PGE2 or RPE-conditioned (PGE2-enriched) media. Endothelial tube formation in HUVECs was increased when co-cultured with PGE2-conditioned CD200R(-/-) BMMΦ, and laser-induced choroidal neovascularization was enhanced in CD200R-deficient mice. In corroboration, signaling through CD200R results in the down-regulation of BMMΦ angiogenic and pro-inflammatory phenotypes. Translational potential of this pathway was investigated in the laser-induced model of choroidal neovascularization. Local delivery of a CD200R agonist mAb to target myeloid infiltrate alters macrophage phenotype and inhibits pro-angiogenic gene expression, which suppresses pathological angiogenesis and CNV development.

Perineural infiltrates in Pseudomonas keratitis.

We describe 2 cases of contact lens-related microbial keratitis caused by infection with Pseudomonas aeruginosa in which perineural infiltrates were observed at presentation. In both cases, examination by confocal microscopy was negative for Acanthamoeba cysts but bacterial cultures and microscopy of corneal scrapings were positive for P aeruginosa. Both cases responded rapidly to treatment with topical levofloxacin with no significant long-term sequelae. These observations indicate that perineural infiltrates may occur in Pseudomonas keratitis without underlying Acanthamoeba infection and are, therefore, not pathognomonic of Acanthamoeba infection.

Assessing a novel depot delivery strategy for noninvasive administration of VEGF/PDGF RTK inhibitors for ocular neovascular disease.

PURPOSE: Two noninvasive delivery strategies for VEGF/PDGF receptor tyrosine kinase inhibitors (RTKI) were explored that exploited uveal retention as a means for establishing an ocular drug depot: a single oral "loading" dose and topical administration. METHODS: Melanin binding was confirmed by centrifugation and mass spectrometry. Ocular retention was examined in pigmented and albino rats. Ocular release kinetics were measured 3 to 28 days postdosing in pigmented rats. Microautoradiography was used to demonstrate retention of RTKI in the uveal tract. A uveal drug depot of pazopanib was created by a single oral dose prior to induction of laser choroidal neovascularization (CNV). Choroid/retinal pigmented epithelium (RPE) retention of a related RTKI with enhanced topical bioavailability, GW771806, was confirmed by bioanalytics, and its ability to regress CNV compared with pazopanib. RESULTS: Pazopanib and GW771806 directly bound melanin and were retained within the uveal tract of pigmented rats for weeks following a single oral dose. Pazopanib was undetectable systemically following a single oral administration prior to CNV induction, and reduced CNV as well as twice daily dosing. Topical ocular delivery of GW771806 at 5 mg/mL led to high choroidal/RPE exposure and significantly regressed CNV lesions; 2 mg/mL prevented lesion progression. CONCLUSIONS: Uveal retention of drugs such as pazopanib can be used to create a sustained-release depot. Topical GW771806 regressed CNV. These data indicate that topical or infrequent oral loading dose treatment with VEGF/PDGF RTKI retained in the choroid/RPE might allow noninvasive treatments for ocular neovascular disease.

Ccl2, Cx3cr1 and Ccl2/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration.

Monocytes, macrophages, dendritic cells and microglia play critical roles in the local immune response to acute and chronic tissue injury and have been implicated in the pathogenesis of age-related macular degeneration. Defects in Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling cause enhanced accumulation of bloated subretinal microglia/macrophages in senescent mice and this phenomenon is reported to result in the acceleration of age-related retinal degeneration. The purpose of this study was to determine whether defects in CCL2-CCR2 and CX3CL1-CX3CR1 signalling pathways, alone or in combination, cause age-dependent retinal degeneration. We tested whether three chemokine knockout mouse lines, Ccl2(-/-), Cx3cr1(-/-) and Ccl2(-/-)/Cx3cr1(-/-), in comparison to age-matched C57Bl/6 control mice show differences in subretinal macrophage accumulation and loss of adjacent photoreceptor cells at 12-14 months of age. All mouse lines are derived from common parental strains and do not carry the homozygous rd8 mutation in the Crb1 gene that has been a major confounding factor in previous reports. We quantified subretinal macrophages by counting autofluorescent lesions in fundus images obtained by scanning laser ophthalmoscopy (AF-SLO) and by immunohistochemistry for Iba1 positive cells. The accumulation of subretinal macrophages was enhanced in Ccl2(-/-), but not in Cx3cr1(-/-) or Ccl2(-/-)/Cx3cr1(-/-) mice. We identified no evidence of retinal degeneration in any of these mouse lines by TUNEL staining or semithin histology. In conclusion, CCL2-CCR2 and/or CX3CL1-CX3CR1 signalling defects may differentially affect the trafficking of microglia and macrophages in the retina during ageing, but do not appear to cause age-related retinal degeneration in mice.