Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

[Isolated primary vitreoretinal lymphoma (case report)]. / Izolirovannaya pervichnaya vitreoretinal'naya limfoma (klinicheskoe nablyudenie).

This case report presents the diagnostic features of isolated primary intraocular lymphoma, which was initially misdiagnosed as neovascular age-related macular degeneration. A comprehensive examination using ultrasound, optical coherence tomography, and fundus autofluorescence revealed changes characteristic of vitreoretinal lymphoma. Molecular genetic analysis of the vitreous body showed the presence of a MYD88 gene mutation and B-cell clonality by immunoglobulin heavy chain (IGH) gene rearrangement tests, which confirmed the diagnosis.

Swept-source optical coherence tomography angiography findings in a case of primary vitreoretinal lymphoma over a three-year follow-up.

BACKGROUND: Vitreoretinal lymphoma (VRL) still represents a diagnostic challenge for retinal specialists. Early diagnosis and treatment are critical for a better prognosis. Several diagnostic tools have proven helpful in the identification of VRL abnormalities. However, swept-source OCT angiography (SS-OCT-A) findings and their long-term follow-up are yet to be explored. CASE PRESENTATION: a 42-year-old man presented with blurred vision in his left eye for 2 weeks. He denied any systemic symptoms. A multimodal imaging examination was performed, raising the clinical suspicion of VRL and guiding the ensuing diagnostic procedures. The patient underwent treatment and at the last FU visit three years later, no disease signs were present on fundus examination, nor on oncologic evaluation. Some novel SS-OCT-A features were identified, and uncommonly reported findings were examined over a long-term follow-up. At baseline multiple hyperreflective alterations were detected on the enface outer retina slabs and choriocapillary analysis revealed low reflectance areas in the foveal and parafoveal areas. One month after the first presentation, multiple hyperreflective retinal lesions in a vertical shape were detected on OCT which appeared on midretinal slabs of enface SS-OCT-A as hyperreflective spots mainly located near second-order retinal vessels. These alterations remarkably reduced after treatment. CONCLUSION: SS-OCT-A may be a useful imaging technique in the detection of VRL, providing ophthalmologists additional findings that assist the diagnosis and follow-up of this disease. This may prove useful for a more timely and precise diagnosis, prompt therapy, and treatment response monitoring. The original aspects found in this case may provide grounds for future studies, ultimately fostering a better understanding of the disease.

Diagnostic methods for primary vitreoretinal lymphoma: A systematic review.

Primary vitreoretinal lymphoma is a potentially aggressive intraocular malignancy with poor systemic prognosis and sometimes significant diagnostic delays as it may masquerade as chronic uveitis. Despite the variety of diagnostic techniques, it is unclear which modality is most accurate in the diagnosis of PVRL. A systematic literature search was conducted on Ovid MEDLINE, EMBASE and the Cochrane Controlled Register of Trials for studies published between January, 2000, and June, 2023. Randomized controlled trials (RCTs) reporting on the following diagnostic tools used to diagnose patients with PVRL were included: cytology, flow cytometry, MYD88 L265P mutation, CD79B mutation, interleukin 10/interleukin-6 (IL-10/IL-6) ratio, polymerase chain reaction (PCR) for monoclonal immunoglobulin heavy chain (IgH) and immunoglobulin kappa light chain (IgK) rearrangements, and imaging findings. The aggregated sensitivity of each diagnostic modality was reported and compared using the chi-squared (χ2) test. A total of 662 eyes from 29 retrospective studies reporting on patients diagnosed with PVRL were included. An IL-10/IL-6 ratio greater than 1 had the highest sensitivity (89.39%, n = 278/311 eyes, n = 16 studies) for PVRL, where the sensitivity was not significantly different when only vitreous samples were drawn (88.89%, n = 232/261 eyes, n = 13 studies) compared to aqueous samples (83.33%, n = 20/24, n = 2) (p = 0.42). Flow cytometry of vitreous samples gave a positive result in 66/75 eyes (88.00%, n = 6 studies) with PVRL, and monoclonal IgH rearrangements on PCR gave a positive result in 354/416 eyes (85.10%, n = 20 studies) with PVRL. MYD88 L265P and CD79B mutation analysis performed poorly, yielding a positive result in 63/90 eyes (70.00%, n = 8 studies) with PVRL, and 20/57 eyes (35.09%, n = 4 studies) with PVRL, respectively. Overall, our systematic review found that an IL-10/IL-6 ratio greater or equal to one may provide the highest sensitivity in identifying patients with PVRL. Future studies are needed to employ multiple diagnostic tools to aid in the detection of PVRL and to further establish nuanced guidelines when determining the optimal diagnostic tool to use in diverse patient populations.

Outcomes and predictive factors in multifocal and extended depth of focus intraocular lens implantation.

PURPOSE OF REVIEW: Options for addressing presbyopia with intraocular lens (IOL) implantation have become more varied and sophisticated. We reviewed recent literature on multifocal and extended depth of focus (EDOF) IOLs in order to provide insight on their respective advantages, with emphasis on the visual outcomes of each design. RECENT FINDINGS: Increased patient age, spectral domain optical coherence tomography (SD-OCT) abnormalities, abnormal optical axis measurements, and better preoperative visual acuity have been implicated as predictors of worse postoperative vision or visual quality in multifocal IOLs. Despite differences in objective outcomes, patient-reported outcomes such as satisfaction are consistently similar between multifocal and EDOF IOLs. EDOFs may have slightly lower rates of spectacle independence than trifocals, but there is more support for their use in the setting of with other ocular conditions. SUMMARY: Multifocal and EDOF IOLs are both viable options for patients who wish to preserve near vision. Given their similar objective performance in many aspects, enabling patients to make informed decisions based on their expectations and visual requirements is critical to postoperative satisfaction. Evidence for advanced technology IOL implantation in pediatric patients remains inconclusive.

PRESUMPTIVE RECURRENCE OF INTRAOCULAR LYMPHOMA DESPITE CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY.

PURPOSE: To present the first reported case of presumptive intraocular recurrence of lymphoma following Chimeric Antigen Receptor (CAR) T-cell therapy despite systemic control by CD19-CAR T cells. METHODS: Observational case report. RESULTS: A 59-year-old man with diffuse, large, B-cell lymphoma subsequently developed secondary central nervous system disease despite chemotherapy. He underwent stem cell transplantation but relapsed again and was scheduled to receive CAR T-cell therapy. He developed vitritis several weeks before treatment, with vitreous biopsy showing non-Hodgkin B-cell lymphoma. He received CAR T-cell therapy following the vitrectomy. He presented 3 months following CAR T-cell therapy with nonspecific right eye floaters and discomfort, with the optical coherence tomography revealing subretinal saw-tooth deposits in the right eye, highly suggestive of lymphoma. This is despite having good systemic control with no other disease elsewhere in the body. He received intravitreal methotrexate to good effect. CONCLUSION: To our knowledge, this is the first case of a vitreoretinal lymphoma nonresponsive to CAR T-cell therapy, despite good central nervous system and systemic control. This is suggestive of anti-CD19 CAR T cells not trafficking into the eye in sufficient numbers to eliminate CD19-expressing neoplastic B cells. We suggest regular ophthalmic follow-up after CAR-T-cell therapy for patients where there is evidence of ocular involvement.

Explantation of a sutureless scleral fixated Carlevale intraocular lens due to calcification: a clinical and laboratory report.

BACKGROUND: Hydrophilic intraocular lens opacification is a rare complication due to calcification. With current new surgical techniques, including lamellar endothelial keratoplasty and vitrectomies, this irreversible complication is becoming more common. In this case study, we present clinical and laboratory features of a case of Carlevale hydrophilic acrylic IOL calcification. CASE PRESENTATION: Observational case report of a single incident case. An 83-year-old man was referred to our ophthalmic department complaining of right eye vision blurring for six months. Slit-lamp biomicroscopy revealed IOL opacification. Deposits of calcium phosphate were found both on the IOL's surface and inside it, according to thorough investigation using optical, scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX) spectrometry. CONCLUSIONS: To the best of our knowledge, this is the first case to describe the laboratory evidence of Carlevale hydrophilic IOL calcification, suggesting possible explanation mechanisms based on underlying pathology and surgical technique. It reminds us that these findings suggest that physicians should be aware of possible hydrophilic IOL calcification.

Results of an Extended Depth-of-Focus Intraocular Lens Implantation in the Second Eye of Monofocal Pseudophakic Patients: A Pilot Study.

PURPOSE: The purpose of this study was to investigate the visual results and patient satisfaction after implantation of an extended depth-of-focus (EDOF) intraocular lens (IOL) in the second eye of patients implanted previously with a monofocal IOL in the first eye. METHODS: The medical records and self-reported questionnaires from patients who were implanted with monofocal IOLs in the first eye and EDOF IOLs in the second eye (group A) and from patients implanted bilaterally with EDOF IOLs (group B) were compared for visual acuity (VA), spectacle independence, patient satisfaction, and photic phenomena. RESULTS: Group A (23 eyes of 23 patients) had similar distance uncorrected VA and intermediate uncorrected VA compared with group B (72 eyes of 36 patients) (0.03±0.05 vs. 0.04±0.16; P =0.136 and 0.660, respectively). There was a tendency toward a better near uncorrected VA in group A compared with group B (0.15±0.14 vs. 0.23±0.17; P =0.074). Patients' perception of their VA was similar between groups. Spectacle independence for distance vision was reported by 16/17 (94.1%) and 35/36 (97.2%) patients ( P =0.543), 13/17 (76.5%) and 32/36 (88.9%) patients ( P =0.252) for intermediate vision, and 4/17 (23.6%) and 22/36 (61.1%) patients for near vision ( P =0.011), in groups A and B, respectively. There was no difference in complaints of photic phenomena between groups. CONCLUSIONS: Patients previously implanted with a monofocal IOL in 1 eye who are interested in improving their spectacle independence can be considered for an EDOF IOL implantation in the second eye and may have similar results to those implanted bilaterally with EDOF IOLs.

Preferred surgical techniques for secondary intraocular lens implantation in adults with aphakia.

AIM: To identify the current surgical management of aphakia and the outcomes and complications of each technique. METHODS: This cross-sectional study included ophthalmic surgeons with at least one-year experience in surgery for aphakia. A study questionnaire was formulated to collect data in Saudi Arabia and other regional countries. The questionnaire included 22 questions on demographics, preferred surgical techniques, complications and the factors related to surgeon decision and the choice for managing aphakia. RESULTS: The study included 145 participants (111; 76.6% were males) with mean age of 46.7 ± 11.5 years. The mean duration of cataract surgery experience was 17.6 ± 11.1 years. Most participants (86.2%) were trained in cataract surgery. Scleral fixation of intraocular lens (SFIOL) was the most commonly preferred technique, followed by iris fixation IOL, and anterior chamber IOL (75.2%, 9%, and 15.9%, respectively). The main determinants for selection of a surgical technique were simplicity (56.6%), surgical instrument availability (48.3%), and training on the technique (47.6%). The most frequent postoperative complications were pupil distortion, high intraocular pressure (IOP), pupillary capture of the IOL, and IOL decentration. CONCLUSIONS: SFIOL is the preferred surgical technique for managing aphakia. The decision to choose one technique over another is complex and is based on several factors, including technical difficulty, previous training, anatomical variations, ocular comorbidities, and the potential complications. The most frequent complications after surgical correction of aphakia are pupil distortion, high IOP, pupillary capture of the IOL, and decentered IOLs.

Clinical outcomes of a new four-haptic hydrophobic presbyopia-correcting intraocular lens.

A new presbyopia-correcting intraocular lens (IOL) combining bifocal and extended-depth-of-focus profiles (Symbiose: Artis Symbiose Plus; Cristalens Industrie, Lannion, France) was introduced. We compared the output with that of a standard monofocal IOL (PL E: Artis PL E). The two four-haptic hydrophobic IOLs were made of the same material from the same company. Cataract patients bilaterally implanted with either PL E or Symbiose between November 2021 and August 2022 were reviewed. The principal measures of the postoperative results were uncorrected distance visual acuity (UDVA); corrected distance VA (CDVA); uncorrected intermediate VA; uncorrected near VA; objective optical quality; and distance-corrected defocus curves. This study included forty-eight patients (96 eyes), with 22 and 26 patients (44 and 52 eyes, respectively) being implanted with PL E and Symbiose, respectively. All patients received the same type of IOL implanted in both eyes. The average age of patients was 70.9 ± 7.1 and 60.0 ± 8.5 years in PL E and Symbiose groups, respectively, with significantly younger patients in Symbiose group (p < 0.001). Both IOLs displayed excellent UDVA and CDVA with no statistical difference (p = 0.081 (monocular UDVA), p = 0.599 (monocular CDVA), p = 0.204 (binocular UDVA), and p = 0.145 (binocular CDVA)). In comparison with PL E group, Symbiose group showed significantly superior postoperative intermediate and near VA (p < 0.001). PL E group showed significantly superior objective optical quality compared with Symbiose group (p < 0.001). Symbiose provides a continuous range of vision that ensures a seamless transition from far to near with no discontinuity. It also delivers a smooth defocus curve with a larger landing area than the PL E. But the objective optical quality was better in PL E.

Diagnosis and management of vitreoretinal lymphoma: present and future treatment perspectives.

Intraocular lymphoma (IOL) is a rare malignant intraocular lymphocytic tumor that mimics uveitis. IOL is anatomically classified into vitreoretinal lymphoma (VRL) and uveal lymphoma; most IOLs are VRLs, while uveal lymphoma is rare. VRL is highly malignant, with 60%-85% of patients developing central nervous system (CNS) lymphoma; primary VRL (PVRL) is an ocular disease with poor prognosis. We aimed to review the management and both current and future treatments for VRL. VRL diagnosis is based on the results of cytopathological examination using vitreous biopsy. However, the positive ratio of vitreous cytology remains 29%-70%. A combination of adjunctive tests may improve diagnostic accuracy, but as yet no gold-standard regimen has been established. Methotrexate intravitreal injections are effective in controlling ocular lesions; however, this treatment allows CNS dissemination. The efficacy of systemic chemotherapy in suppressing CNS dissemination has been recently debated. A multicenter prospective study with a unified treatment protocol is required to clarify this issue. In addition, establishing a treatment protocol for elderly patients and those with poor general health is necessary. Moreover, relapsed/refractory VRL and secondary VRL are more difficult to treat than PVRL because they are prone to recurrence. Ibrutinib, lenalidomide with or without rituximab, and temozolomide are promising treatments for relapsed/refractory VRL. In Japan, Bruton's tyrosine kinase (BTK) inhibitors have been approved for treating refractory CNS lymphoma. Furthermore, a randomized prospective study of tirabrutinib, a highly selective BTK inhibitor, is ongoing for evaluating the suppressing of CNS progression in patients with PVRL.

DIAGNOSTIC YIELD OF IN VITRO VITREOUS BIOPSY FOR INTRAOCULAR LYMPHOMA AT VARIABLE VITREOUS CUTTER SPEEDS USING 25-GAUGE VITRECTOMY.

PURPOSE: Primary vitreoretinal lymphoma is the most common intraocular lymphoproliferative disorder. We evaluated the diagnostic yield of pars plana vitrectomy, specifically using modern high cut rate dual-cycle cutters, on in vitro cell viability and diagnostic yield. METHODS: Human Burkitt lymphoma cell line Namalwa at 2 x 10^5 cells/mL was aspirated by 25-gauge dual-blade guillotine-type vitrectomy at five speeds (500, 1,000, 4,000, 7,500, or 15,000 cuts per minute). Cell viability and diagnostic yield in each subtype group were determined using hemocytometry, viable cell count using Cell Counting Kit-8, and pathologist-guided manual count. RESULTS: No significant deviation in cell count was identified in any cut rate by ANOVA ( P = 0.61), and no trends in the number of viable cells were identified across cut rates (R 2 = 0.188, P = 0.47). Among histologic cell counts per cut-rate, neither linear regression (R = 0.531, P = 0.16) nor ANOVA ( P = 0.096) were statistically significant. CONCLUSION: There was no significant degradation in the number of viable cells with increasing cut speed. These results suggest that in contrast to previous findings using 20g or 23g vitrectomy for diagnostic vitrectomy, modern vitrectomy systems may be used at up to 15,000 cpm without compromising the viability of lymphoma cells.

Diagnosis, treatment, and prognosis of primary intraocular lymphoma: Single-center real-world clinical experience.

BACKGROUND: The diagnosis and management of primary intraocular lymphoma (PIOL) remain challenging. This study identified factors indicative of PIOL, described treatment outcomes, and determined modalities to prevent relapse. METHODS: We included 21 PIOL-diagnosed patients, seven via cytology, 12 via genetic evaluation, and two via interleukin (IL) level measurements, who underwent vitrectomy and received local intravitreal methotrexate (IV-MTX) injection. Clinical outcomes, including treatment response and relapse, were compared between patients receiving IV-MTX alone (n = 13) or IV-MTX with systemic high-dose methotrexate (HD-MTX) as prophylaxis (n = 8). RESULTS: Twelve ophthalmologic and eight central nervous system (CNS) relapse cases within a median of 20.3 and 11.6 months were shown, regardless of the treatment modalities, with a median progression-free survival of 21.3 (95% confidence interval, 9.5-36.7) months. There was no difference in demographic characteristics between the two groups, except with the poorer performance status in patients in the HD-MTX prophylaxis group. Furthermore, patients demonstrated rapid elevations in the vitreous fluid IL-10/IL-6 cytokine ratio before ophthalmologic and CNS relapse. Therefore, diagnosis should be based on clinical signs and assisted by vitrectomy, cytologic, molecular, and cytokine studies. CONCLUSION: For PIOL, aggressive systemic treatment equivalent to that of primary CNS lymphoma (PCNSL) is recommended because solely HD-MTX did not prevent or delay CNS relapse. To prevent PIOL relapse in the CNS efficiently, prospective trials with large numbers of patients and advanced therapeutic regimens are necessary. Furthermore, regular clinical follow-up is crucial, and the IL-10/IL-6 ratio can help evaluate relapse promptly.

UTILITY OF EN FACE OPTICAL COHERENCE TOMOGRAPHY IN INTRAOCULAR LYMPHOMA.

PURPOSE: To report the en face optical coherence tomography (OCT) features of intraocular lymphoma. METHODS: Retrospective, observational case report. RESULTS: A 59-year-old man, a known case of primary testicular carcinoma, complained of right eye blurred vision since 1 week. He had previously undergone systemic intravenous chemotherapy (R-CHOP regimen), orchiectomy, and external beam radiotherapy for the primary malignancy. His right eye vision was 20/30, 6/6 reduced Snellen. The right eye anterior segment examination was normal. Fundus examination showed vitreous cells 1+ and a large, bumpy, subretinal dull-yellow lesion sparing the fovea with multiple discrete yellow retinal lesions at the posterior pole. Magnetic resonance imaging of the brain was normal. Multimodal imaging was used to document the clinical features. On the en face OCT, multiple hyperreflective lesions were identified on the superficial, deep, and outer retinal slabs of the scan corresponding to the vertical hyperreflective lesions extending from the retinal nerve fiber layer to the retinal pigment epithelium. The subretinal pigment epithelium lesion can be well delineated in the choriocapillaris segment. He was treated with multiple injections of intravitreal methotrexate 400 µg/0.1 mL along with systemic chemotherapy in conjunction with the oncologist. At the 6-month follow-up, fundus lesions had regressed. In addition, resolution of the lesions was noted on the OCT and en face OCT scans. CONCLUSION: En face OCT imaging can be considered for monitoring the therapeutic efficacy after intravitreal chemotherapy in intraocular lymphoma.

Intraocular Metastasis of Large T-cell Lymphoma Transformed from Mycosis Fungoides.

PURPOSE: To describe a rare case of intraocular lymphoma that metastasized from cutaneous mycosis fungoides and transformed to large cell T cell lymphoma resulting in vitreoretinal pathology. METHODS: Retrospective case report. RESULTS: A 57-year-old male presented with 3 months of blurred vision in the right eye. He reported only a medical history of psoriasis. Examination revealed keratic precipitates and dense vitritis in the right eye. He was taken for a diagnostic vitrectomy. Histopathology showed that atypical lymphoid cells and flow cytometry were consistent with transformed large cell T-cell lymphoma. During follow-up, pre- and inner retinal lesions were noted throughout the posterior pole. Histopathology of the psoriatic lesions was consistent with mycosis fungoides. He was initiated on systemic and intravitreal methotrexate with improvement in vision. CONCLUSIONS: Ocular involvement in metastatic transformed T-cell lymphoma is extremely rare but can be present with vitritis and retinal deposits. Our patient responded well to intravitreal methotrexate therapy.

One-dioptre toric IOL versus spherical IOL in eyes with low preoperative corneal astigmatism.

PURPOSE: To investigate the advantages/disadvantages of a 1.0 D toric IOL vs spherical IOL after regular phacoemulsification in eyes with preoperative astigmatism ≤ 1 D. METHODS: Retrospective comparative series involving pseudophakic eyes with preoperative topographic astigmatism ≤ 1.0 D implanted either with monofocal 1.0 D Toric IOL (T-group), or with spherical IOL (S-group). The postoperative refractive astigmatism (PRA, i.e. surgically induced + corneal) was the main outcome; also considered in the analyses were the uncorrected and best-corrected distance visual acuity (VA). The data were referred to the last postoperative follow-up visit, 2 to 4 months after surgery. RESULTS: A total of 60 eyes were included: 30 in the T-group and 30 in the S-group, matched for patient's age, laterality, and axial length. Before surgery, the mean corneal astigmatism was 0.62 ± 0.39 D in the T-group and 0.54 ± 0.33 D in the S-group (p = 0.4). In the S-group, PRA was 0.73 ± 0.37 D, higher than the corresponding preoperative corneal astigmatism (p = 0.040). In the T-group, PRA was 0.58 ± 0.31 D; the variation was not statistically significant. Uncorrected VA was significantly better in the T-group vs the S-group (p = 0.007), and the best-corrected VA was comparable in the two groups. CONCLUSION: The present study indicated that in eyes with very low preoperative astigmatism, 1.0 D toric IOLs were able to limit the increase of the PRA instead of those observed with the spherical IOLs. This could support the better uncorrected VA recorded in the T-group.